bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world sentence boundary detection using multitask learning: A case study on French
Authors: Lim KyungTae , Park Jungyeul
Published: April 2022

We propose a novel approach for sentence boundary detection in text datasets in which boundaries are not evident (e.g., sentence fragments). Although detecting sentence boundaries without punctuation marks has rarely been explored in written text, current real-world textual data suffer from widespread lack of proper start/stop signaling. Herein, we annotate a dataset with linguistic information, such as parts of speech and named entity labels, to boost the sentence boundary detection task. Via experiments, we obtained F1 scores up to 98.07% using the proposed multitask neural model, including a score of 89.41% for sentences completely lacking punctuation marks. We also present an ablation study and provide a detailed analysis to demonstrate the effectiveness of the proposed multitask learning method.
James Stirling’s post-avant-garde collage: the flatbed picture plane & the pursuit of virtuality
Authors: Proto Francesco
Published: April 2022

The second decade of the twenty-first century has been distinguished by a renewed interest in James Stirling and his architectural heritage – a sort of ‘James Stirling Renaissance’ – with many authors characterising Stirling predominantly as a late modernist architect.
Value-based evidence across health care sectors: a push for transparent real-world studies, data, and evidence dissemination
Authors: van den Broek Remon W. M. , Matheis Robert J. , Bright Jennifer L. , Hartog Tessa E. , Perfetto Eleanor M.
Published: April 2022

There is currently a heightened need for transparency in pharmaceutical sectors. The inclusion of real-world (RW) evidence, in addition to clinical trial evidence, in decision-making processes, was an important step forward toward a more inclusive established value proposition. This advance has introduced new transparency challenges. Increasing transparency is a critical step toward accelerating improvement in type, quality, and access to data, regardless of whether these originate from clinical trials or from RW studies. However, so far, advances in transparency have been relatively restricted to clinical trials, and there remains a lack of similar expectations or standards of transparency concerning the generation and reporting of RW data. This perspective paper aims to highlight the need for transparency concerning RW studies, data, and evidence across health care sectors, to identify areas for improvement, and provide concrete recommendations and practices for the future. Specific issues are discussed from different stakeholder perspectives, culminating in recommended actions, from individual stakeholder perspectives, for improved RW study, data, and evidence transparency. Furthermore, a list of potential guidelines for consideration by stakeholders is proposed. While recommendations from different stakeholder perspectives are made, true transparency in the processes involved in the generation, reporting, and use of RW evidence will require a concerted effort from all stakeholders across health care sectors.
In or against the state? Hospitality and hostility in homelessness charities and deportation practice
Authors: Dobson Rachael , Turnbull Sarah
Published: April 2022

This paper examines how deportation became a solution to rough sleeping in pre-Brexit England. It identifies relationships between the social regulation of vulnerable and marginalised adults, contemporary governance arrangements and bordering practices characteristic of Britain's ‘hostile environment’. Drawing on media reports and grey organisational literature, the focus of discussion is events across 2015–2018 in which three London-based charities were criticised for working with the Home Office to deport homeless migrants under its European Economic Area Administrative Removal policy. The overall tenor of criticism was that collaboration with the government compromised the organisations’ independence and charitable missions and aims. This diminished their capacity to both advocate for vulnerable adults and effectively challenge oppressive state practices. The paper observes how state and nonprofit relations structure institutional and socio-legal responses to marginalised and ‘othered’ adults through commissioning and contracting mechanisms. It demonstrates that the social and legal control of homeless migrants may be differently constituted by institutions delivering services in relation to citizenship, vulnerability and marginalisation. This analysis incorporates a broader appraisal of institutional motivations, values and beliefs in social welfare delivery, including the historic role of charitable agencies in the criminalisation of social welfare users. Taken together, the paper offers an interdisciplinary critique of the relationships between border control, neoliberal governance and the sociocultural and historic construction of homeless migrants.
Have News Reports on Suicide and Attempted Suicide During the COVID-19 Pandemic Adhered to Guidance on Safer Reporting?
Authors: Marzano Lisa , Hawley Monica , Fraser Lorna , Harris-Skillman Eva , Lainez Yasmine , Hawton Keith
Published: April 2022

Abstract. Background: Associations between sensational news coverage of suicide and increases in suicidal behavior have been well documented. Amid growing concern over the impact of the COVID-19 pandemic on suicide rates, it is especially important that news coverage adheres to recommended standards. Method: We analyzed the quality and content of print and online UK news reports of possible COVID-19-related suicides and suicide attempts in the first 4 months of the pandemic ( N = 285). Results: The majority of reports made explicit links between suicidal behavior and the COVID-19 pandemic in the headline (65.5%), largely based on statements by family, friends, or acquaintances of the deceased (60%). The impact of the pandemic on suicidal behavior was most often attributed to feelings of isolation (27.4%), poor mental health (14.7%), and entrapment due to government-imposed restrictions (14.4%). Although rarely of poor overall quality, reporting was biased toward young people, frontline staff, and relatively unusual suicides and, to varying degrees, failed to meet recommended standards (e.g., 41.1% did not signpost readers to sources of support). Limitations: This analysis cannot account for the impact of reporting on suicide. Conclusion: Careful attention must be paid to the quality and content of reports, especially as longer-term consequences of the pandemic develop.
Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia
Authors: Yeom Eunbyul , Yu Kweon
Published: April 2022

Cancer cachexia syndrome is a major cause of morbidity and mortality in cancer patients in the advanced stage. It is a devastating disorder characterized by nutritional impairment, weakness, and wasting, and it affects treatment success and quality of life. Two major symptoms of cancer cachexia are anorexia and weight loss. Weight loss in cachexia is not reversed through increased food intake, suggesting that anorexia and weight loss in cancer patients are regulated by independent molecular mechanisms. Although the wasting phenotype mostly occurs in skeletal muscle and adipose tissue, other organs, such as the brain, liver, pancreas, heart, and gut, are also involved in cachexia. Thus, cachexia is a multiorgan syndrome. Although the molecular basis of cancer cachexia-induced weight loss is known, the mechanism underlying anorexia is poorly understood. Here, we highlight our recent discovery of a new anorexia mechanism by which a tumor-derived humoral factor induces cancer anorexia by regulating feeding-related neuropeptide hormones in the brain. Furthermore, we elucidated the process through which anorexia precedes tissue wasting in cachexia. This review article aims to provide an overview of the key molecular mechanisms of anorexia and tissue wasting caused by cancer cachexia.
A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling
Authors: Qin Yue , Du Yasong , Chen Liqiang , Liu Yanyan , Xu Wenjing , Liu Ying , Li Ying , Leng Jing , Wang Yalan , Zhang Xiao-Yong , Feng Jianfeng , Zhang Feng , Jin Li , Qiu Zilong , Gong Xiaohong , Wang Hongyan
Published: April 2022

The genetic etiology and underlying mechanism of autism spectrum disorder (ASD) remain elusive. SHANK family genes (SHANK1/2/3) are well known ASD-related genes. However, little is known about how SHANK missense mutations contribute to ASD. Here, we aimed to clarify the molecular mechanism of and the multilevel neuropathological features induced by Shank1 mutations in knock-in (KI) mice. In this study, by sequencing the SHANK1 gene in a cohort of 615 ASD patients and 503 controls, we identified an ASD-specific recurrent missense mutation, c.2621 G > A (p.R874H). This mutation demonstrated strong pathogenic potential in in vitro experiments, and we generated the corresponding Shank1 R882H-KI mice. Shank1 R882H-KI mice displayed core symptoms of ASD, namely, social disability and repetitive behaviors, without confounding comorbidities of abnormal motor function and heightened anxiety. Brain structural changes in the frontal cortex, hippocampus and cerebellar cortex were observed in Shank1 R882H-KI mice via structural magnetic resonance imaging. These key brain regions also showed severe and consistent downregulation of mGluR1-IP3R1-calcium signaling, which subsequently affected the release of intracellular calcium. Corresponding cellular structural and functional changes were present in Shank1 R882H-KI mice, including decreased spine size, reduced spine density, abnormal morphology of postsynaptic densities, and impaired hippocampal long-term potentiation and basal excitatory transmission. These findings demonstrate the causative role of SHANK1 in ASD and elucidate the underlying biological mechanism of core symptoms of ASD. We also provide a reliable model of ASD with core symptoms for future studies, such as biomarker identification and therapeutic intervention studies.
Engineering strategies to enhance oncolytic viruses in cancer immunotherapy
Authors: Tian Yaomei , Xie Daoyuan , Yang Li
Published: April 2022

Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed. In addition to direct oncolysis, the essential and attractive aspect of oncolytic virotherapy is based on the intrinsic induction of both innate and adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered to express immune regulators that enhance or restore antitumor immunity. Recently, combinations of OVs with other immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptors (CARs), antigen-specific T-cell receptors (TCRs) and autologous tumor-infiltrating lymphocytes (TILs), have led to promising progress in cancer treatment. This review summarizes the intrinsic mechanisms of OVs, describes the optimization strategies for using armed OVs to enhance the effects of antitumor immunity and highlights rational combinations of OVs with other immunotherapies in recent preclinical and clinical studies.
LncRNA HOXC-AS3 promotes non-small-cell lung cancer growth and metastasis through upregulation of YBX1
Authors: Su HongBo , Fan GuanZhi , Huang Jin , Qiu XueShan
Published: April 2022

NSCLC is common and is the primary cause of cancer-related deaths due to a lack of early diagnosis and its propensity for metastasis. The pathogenesis of NSCLC is still unclear. Here, we explored the molecular mechanisms underlying NSCLC development, focusing on the HOXC-AS3/YBX1/HOXC8 axis. Human NSCLC specimens and cell lines were used. qRT-PCR and western blotting were utilised to examine the levels of HOXC-AS3/YBX1/HOXC8. CCK-8, colony formation, scratch wound healing and Transwell assays were performed to evaluate cancer cell proliferation, migration and invasion. A nude mouse xenograft model was used to examine tumour growth and metastasis in vivo. RNA pull-down, chromatin immunoprecipitation, coimmunoprecipitation and dual-luciferase assays were applied to validate the interactions of HOXC-AS3/YBX1, MDM2/YBX1 and the YBX1/HOXC8 promoter. The levels of HOXC-AS3 and HOXC8 were increased in human NSCLC specimens and cells. Knockdown of HOXC-AS3 suppressed NSCLC cell proliferation, migration and invasion, as well as tumour growth and metastasis in vivo. HOXC-AS3 directly bound to YBX1 to suppress its ubiquitination mediated by MDM2. YBX1 bound to the HOXC8 promoter and enhanced its transcription. Knockdown of HOXC8 inhibited the effects of HOXC-AS3 overexpression on NSCLC. HOXC-AS3 promotes NSCLC growth and metastasis by stabilising YBX1 and thus increasing HOXC8 transcription. Our study indicates that the HOXC-AS3/YBX1/HOXC8 axis could serve as a biomarker for NSCLC diagnosis or as a target for therapy development.
Stabilization of parameter estimates from multiexponential decay through extension into higher dimensions
Authors: Bi Chuan , Fishbein Kenneth , Bouhrara Mustapha , Spencer Richard G.
Published: April 2022

Analysis of multiexponential decay has remained a topic of active research for over 200 years. This attests to the widespread importance of this problem and to the profound difficulties in characterizing the underlying monoexponential decays. Here, we demonstrate the fundamental improvement in stability and conditioning of this classic problem through extension to a second dimension; we present statistical analysis, Monte-Carlo simulations, and experimental magnetic resonance relaxometry data to support this remarkable fact. Our results are readily generalizable to higher dimensions and provide a potential means of circumventing conventional limits on multiexponential parameter estimation.
An ambient air quality evaluation model based on improved evidence theory
Authors: Sun Qiao , Zhang Tong , Wang Xinyang , Lin Weiwei , Fong Simon , Chen Zhibo , Xu Fu , Wu Ling
Published: April 2022

It is significant to evaluate the air quality scientifically for the management of air pollution. As an air quality comprehensive evaluation problem, its uncertainty can be effectively addressed by the Dempster–Shafer (D–S) evidence theory. However, there is not enough research on air quality comprehensive assessment using D–S theory. Aiming at the counterintuitive fusion results of the D–S combination rule in the field of comprehensive decision, an improved evidence theory with evidence weight and evidence decision credibility (here namely DCre-Weight method) is proposed, and it is used to comprehensively evaluate air quality. First, this method determines the weights of evidence by the entropy weight method and introduces the decision credibility by calculating the dispersion of different evidence decisions. An algorithm case shows that the credibility of fusion results is improved and the uncertainty is well expressed. It can make reasonable fusion results and solve the problems of D–S. Then, the air quality evaluation model based on improved evidence theory (here namely the DCreWeight model) is proposed. Finally, according to the hourly air pollution data in Xi’an from June 1, 2014, to May 1, 2016, comparisons are made with the D–S, other improved methods of evidence theory, and a recent fuzzy synthetic evaluation method to validate the effectiveness of the model. Under the national AQCI standard, the MAE and RMSE of the DCreWeight model are 1.02 and 1.17. Under the national AQI standard, the DCreWeight model has the minimal MAE, RMSE, and maximal index of agreement, which validated the superiority of the DCreWeight model. Therefore, the DCreWeight model can comprehensively evaluate air quality. It can provide a scientific basis for relevant departments to prevent and control air pollution.
Low molecular weight polysialic acid binds to properdin and reduces the activity of the alternative complement pathway
Authors: Shahraz Anahita , Lin Yuchen , Mbroh Joshua , Winkler Jonas , Liao Huan , Lackmann Marie , Bungartz Annemarie , Zipfel Peter F. , Skerka Christine , Neumann Harald
Published: April 2022

Sialic acids as the terminal caps of the cellular glycocalyx play an essential role in self-recognition and were shown to modulate complement processes via interaction between α2,3-linked sialic acids and complement factor H. Previously, it was suggested that low molecular weight α2,8-linked polysialic acid (polySia avDP20) interferes with complement activation, but the exact molecular mechanism is still unclear. Here, we show that soluble polySia avDP20 (molecular weight of ~ 6 kDa) reduced the binding of serum-derived alternative pathway complement activator properdin to the cell surface of lesioned Hepa-1c1c7 and PC-12 neuroblastoma cells. Furthermore, polySia avDP20 added to human serum blocked the alternative complement pathway triggered by plate-bound lipopolysaccharides. Interestingly, no inhibitory effect was observed with monosialic acid or oligosialic acid with a chain length of DP3 and DP5. In addition, polySia avDP20 directly bound properdin, but not complement factor H. These data show that soluble polySia avDP20 binds properdin and reduces the alternative complement pathway activity. Results strengthen the previously described concept of self-recognition of sialylation as check-point control of complement activation in innate immunity.
Naturally occurring combinations of receptors from single cell transcriptomics in endothelial cells
Authors: Domanskyi Sergii , Hakansson Alex , Meng Michelle , Pham Benjamin K. , Graff Zivin Joshua S. , Piermarocchi Carlo , Paternostro Giovanni , Ferrara Napoleone
Published: April 2022

VEGF inhibitor drugs are part of standard care in oncology and ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for more effective therapies of angiogenesis-related diseases. In this paper we describe naturally occurring combinations of receptors in endothelial cells that might help to understand how cells communicate and to identify targets for drug combinations. We also develop and share a new software tool called DECNEO to identify them. Single-cell gene expression data are used to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and humans) and enriched, within a network, of connections to up-regulated genes. This set includes several receptors previously shown to play a role in angiogenesis. Multiple statistical tests from large datasets, including an independent validation set, support the reproducibility, evolutionary conservation and role in angiogenesis of these naturally occurring combinations of receptors. We also show tissue-specific combinations and, in the case of choroid endothelial cells, consistency with both well-established and recent experimental findings, presented in a separate paper. The results and methods presented here advance the understanding of signaling to endothelial cells. The methods are generally applicable to the decoding of intercellular combinations of signals.
An analysis of student essays on medical leadership and its educational implications in South Korea
Authors: Lee I Re , Jung Hanna , Lee Yewon , Shin Jae Il , An Shinki
Published: April 2022

To examine medical students’ perceptions of leadership and explore their implications for medical leadership education. We conducted a qualitative analysis of the essays submitted by students in the medical leadership course from 2015 to 2019. We categorised the essays by the characteristics of the selected model leaders (N = 563) and types of leadership (N = 605). A statistically significant proportion of students selected leaders who were of the same gender as themselves (P < 0.001), graduate track students chose leaders in science (P = 0.005), while; military track students chose leaders in the military (P < 0.001). Although the highest proportion of students chose politicians as their model leaders (22.7%), this number decreased over time (P < 0.001), and a wider range of occupational groups were represented between 2015 and 2019. Charismatic leadership was the most frequently selected (31.9%), and over time there was a statistically significant (P = 0.004) increase in the selection of transformational leadership. Students tended to choose individuals whose acts of leadership could be seen and applied. Medical leadership education should account for students’ changing perceptions and present a feasible leadership model, introducing specific examples to illustrate these leadership skills.
Hierarchical multi-label classification based on LSTM network and Bayesian decision theory for LncRNA function prediction
Authors: Feng Shou , Li Huiying , Qiao Jiaqing
Published: April 2022

Growing evidence shows that long noncoding RNAs (lncRNAs) play an important role in cellular biological processes at multiple levels, such as gene imprinting, immune response, and genetic regulation, and are closely related to diseases because of their complex and precise control. However, most functions of lncRNAs remain undiscovered. Current computational methods for exploring lncRNA functions can avoid high-throughput experiments, but they usually focus on the construction of similarity networks and ignore the certain directed acyclic graph (DAG) formed by gene ontology annotations. In this paper, we view the function annotation work as a hierarchical multilabel classification problem and design a method HLSTMBD for classification with DAG-structured labels. With the help of a mathematical model based on Bayesian decision theory, the HLSTMBD algorithm is implemented with the long-short term memory network and a hierarchical constraint method DAGLabel. Compared with other state-of-the-art algorithms, the results on GOA-lncRNA datasets show that the proposed method can efficiently and accurately complete the label prediction work.
Monitoring of SARS-CoV-2 antibodies using dried blood spot for at-home collection
Authors: Miesse Peyton K. , Collier Bradley B. , Grant Russell P.
Published: April 2022

The utilization of vaccines to fight the spread of SARS-CoV-2 has led to a growing need for expansive serological testing. To address this, an EUA approved immunoassay for detection of antibodies to SARS-CoV-2 in venous serum samples was investigated for use with dried blood spot (DBS) samples. Results from self-collected DBS samples demonstrated a 98.1% categorical agreement to venous serum with a correlation (R) of 0.9600 while professionally collected DBS samples demonstrated a categorical agreement of 100.0% with a correlation of 0.9888 to venous serum. Additional studies were performed to stress different aspects of at-home DBS collection, including shipping stability, effects of interferences, and other sample-specific robustness studies. These studies demonstrated a categorical agreement of at least 95.0% and a mean bias less than ± 20.0%. Furthermore, the ability to track antibody levels following vaccination with the BioNTech/Pfizer vaccine was demonstrated with serial self-collected DBS samples from pre-dose (Day 0) out to 19 weeks.
Mapping the wildland-urban interface in California using remote sensing data
Authors: Li Shu , Dao Vu , Kumar Mukesh , Nguyen Phu , Banerjee Tirtha
Published: April 2022

Due to the mixed distribution of buildings and vegetation, wildland-urban interface (WUI) areas are characterized by complex fuel distributions and geographical environments. The behavior of wildfires occurring in the WUI often leads to severe hazards and significant damage to man-made structures. Therefore, WUI areas warrant more attention during the wildfire season. Due to the ever-changing dynamic nature of California’s population and housing, the update frequency and resolution of WUI maps that are currently used can no longer meet the needs and challenges of wildfire management and resource allocation for suppression and mitigation efforts. Recent developments in remote sensing technology and data analysis algorithms pose new opportunities for improving WUI mapping methods. WUI areas in California were directly mapped using building footprints extracted from remote sensing data by Microsoft along with the fuel vegetation cover from the LANDFIRE dataset in this study. To accommodate the new type of datasets, we developed a threshold criteria for mapping WUI based on statistical analysis, as opposed to using more ad-hoc criteria as used in previous mapping approaches. This method removes the reliance on census data in WUI mapping, and does not require the calculation of housing density. Moreover, this approach designates the adjacent areas of each building with large and dense parcels of vegetation as WUI, which can not only refine the scope and resolution of the WUI areas to individual buildings, but also avoids zoning issues and uncertainties in housing density calculation. Besides, the new method has the capability of updating the WUI map in real-time according to the operational needs. Therefore, this method is suitable for local governments to map local WUI areas, as well as formulating detailed wildfire emergency plans, evacuation routes, and management measures.
Extensive epigenetic modification with large-scale chromosomal and plasmid recombination characterise the Legionella longbeachae serogroup 1 genome
Authors: Slow Sandy , Anderson Trevor , Murdoch David R. , Bloomfield Samuel , Winter David , Biggs Patrick J.
Published: April 2022

Legionella longbeachae is an environmental bacterium that is the most clinically significant Legionella species in New Zealand (NZ), causing around two-thirds of all notified cases of Legionnaires’ disease. Here we report the sequencing and analysis of the geo-temporal genetic diversity of 54 L. longbeachae serogroup 1 (sg1) clinical isolates, derived from cases from around NZ over a 22-year period, including one complete genome and its associated methylome. The 54 sg1 isolates belonged to two main clades that last shared a common ancestor between 95 BCE and 1694 CE. There was diversity at the genome-structural level, with large-scale arrangements occurring in some regions of the chromosome and evidence of extensive chromosomal and plasmid recombination. This includes the presence of plasmids derived from recombination and horizontal gene transfer between various Legionella species, indicating there has been both intra- and inter-species gene flow. However, because similar plasmids were found among isolates within each clade, plasmid recombination events may pre-empt the emergence of new L. longbeachae strains. Our complete NZ reference genome consisted of a 4.1 Mb chromosome and a 108 kb plasmid. The genome was highly methylated with two known epigenetic modifications, m4C and m6A, occurring in particular sequence motifs within the genome.
Efficacy and safety of the sofosbuvir/velpatasvir combination for the treatment of patients with early mild to moderate COVID-19
Authors: Messina Vincenzo , Nevola Riccardo , Izzi Antonio , De Lucia Sposito Pellegrino , Marrone Aldo , Rega Roberto , Fusco Raffaele , Lumino Paolina , Rinaldi Luca , Gaglione Pasqualina , Simeone Filomena , Sasso Ferdinando Carlo , Maggi Paolo , Adinolfi Luigi Elio
Published: April 2022

SARS-CoV-2 is still a health problem worldwide despite the availability of vaccines. Therefore, there is a need for effective and safe antiviral. SARS-CoV-2 and HCV necessitate RNA-dependent RNA polymerase (RdRp) for replication; therefore, it has been hypothesized that RdRp inhibitors used to treat HCV may be effective treating SARS-CoV-2. Accordingly, we evaluated the effect of the sofosbuvir/velpatasvir (SOF/VEL) combination in early SARS-CoV-2 infection. A multicenter case–control study was conducted, enrolling 120 patients with mild or moderate COVID-19, of whom 30, HCV coinfected or not, received SOF/VEL tablets (400/100 mg) once daily for 9 days within a median of 6 days from the beginning of infection and 90 controls were treated with standard care. The primary endpoint was the effect on viral clearance, and the secondary endpoint was the improvement of clinical outcomes. Nasal swabs for SARS-CoV-2 by PCR were performed every 5–7 days. Between 5–14 days after starting SOF/VEL treatment, SAS-CoV-2 clearance was observed in 83% of patients, while spontaneous clearance in the control was 13% (p < 0.001). An earlier SARS-CoV-2 clearance was observed in the SOF/VEL group than in the control group (median 14 vs 22 days, respectively, p < 0.001) also when the first positivity was considered. None of the patients in the SOF/VEL group showed disease progression, while in the control group, 24% required more intensive treatment (high flow oxygen or noninvasive/invasive ventilation), and one patient died (p < 0.01). No significant side effects were observed in the SOF/VEL group. Early SOF/VEL treatment in mild/moderate COVID-19 seems to be safe and effective for faster elimination of SARS-CoV-2 and to prevent disease progression.
Prolonged treatment with the proteasome inhibitor MG-132 induces apoptosis in PC12 rat pheochromocytoma cells
Authors: Tarjányi Oktávia , Haerer Julian , Vecsernyés Mónika , Berta Gergely , Stayer-Harci Alexandra , Balogh Bálint , Farkas Kornélia , Boldizsár Ferenc , Szeberényi József , Sétáló György
Published: April 2022

Rat pheochromocytoma (PC12) cells were treated with the proteasome inhibitor MG-132 and morphological changes were recorded. Initially, neuronal differentiation was induced but after 24 h signs of morphological deterioration became apparent. We performed nuclear staining, flow cytometry and WST-1 assay then analyzed signal transduction pathways involving Akt, p38 MAPK (Mitogen-Activated Protein Kinase), JNK (c-Jun N-terminal Kinase), c-Jun and caspase-3. Stress signaling via p38, JNK and c-Jun was active even after 24 h of MG-132 treatment, while the survival-mediating Akt phosphorylation declined and the executor of apoptosis (caspase-3) was activated by that time and apoptosis was also observable. We examined subcellular localization of stress signaling components, applied kinase inhibitors and dominant negative H-Ras mutant-expressing PC12 cells in order to decipher connections of stress-mediating pathways. Our results are suggestive of that treatment with the proteasome inhibitor MG-132 has a biphasic nature in PC12 cells. Initially, it induces neuronal differentiation but prolonged treatments lead to apoptosis.
Towards automation of the polyol process for the synthesis of silver nanoparticles
Authors: Wolf Jakob B. , Stawski Tomasz M. , Smales Glen J. , Thünemann Andreas F. , Emmerling Franziska
Published: April 2022

Metal nanoparticles have a substantial impact across different fields of science, such as photochemistry, energy conversion, and medicine. Among the commonly used nanoparticles, silver nanoparticles are of special interest due to their antibacterial properties and applications in sensing and catalysis. However, many of the methods used to synthesize silver nanoparticles often do not result in well-defined products, the main obstacles being high polydispersity or a lack of particle size tunability. We describe an automated approach to on-demand synthesis of adjustable particles with mean radii of 3 and 5 nm using the polyol route. The polyol process is a promising route for silver nanoparticles e.g., to be used as reference materials. We characterised the as-synthesized nanoparticles using small-angle X-ray scattering, dynamic light scattering and further methods, showing that automated synthesis can yield colloids with reproducible and tuneable properties.
Experimental study and analytical model for the pore structure of epoxy latex-modified mortar
Authors: Li Pengfei , Lu Wei , An Xuehui , Zhou Li , Han Xun , Du Sanlin , Wang Chengzhi
Published: April 2022

Concrete repair and rehabilitation prolong the effective service lives of structures and are important topics in the building field worldwide. Epoxy latex-modified cementitious materials have shown promise for a number of applications in building and construction, but the mix design processes remain arbitrary because their pore structures are not well understood. Porosity and pore size distributions are pore structure parameters that have direct effects on the mechanical properties and durability of concrete. In this paper, mercury intrusion porosimetry (MIP) was used to analyze the porosities and pore size distributions of epoxy latex-modified mortars. The effects of the polymer-to-cement ratio on the pore structures of epoxy latex-modified mortars were investigated. Mortars with polymer-to-cement ratios of 0%, 5%, 10%, 15%, and 20% were cured for 7, 28, 60, and 90 days in this study. Images of specimen microstructures were obtained by scanning electron microscopy (SEM), which showed that increases in the amount of epoxy latex added caused the proportion of micropores in the mortar to decrease, while the proportion of macropores and gel pores increased. The pore size distribution of epoxy latex-modified mortar was described with a composite logarithmic model. Relationships between the pore size distribution and the polymer-to-cement ratio and the curing age were obtained. The method described herein might be sufficiently accurate and convenient to evaluate or predict the pore size distribution of an epoxy latex-modified mortar, i.e., by determining the statistical distribution and analyzing the probability. The process for design of the polymer concrete mix ratio will be facilitated by methods that accurately describe the structure of the epoxy latex-modified mortar.
Single-cell transcriptome analysis reveals aberrant stromal cells and heterogeneous endothelial cells in alcohol-induced osteonecrosis of the femoral head
Authors: Liao Zheting , Jin Yu , Chu Yuhao , Wu Hansen , Li Xiaoyu , Deng Zhonghao , Feng Shuhao , Chen Nachun , Luo Ziheng , Zheng Xiaoyong , Bao Liangxiao , Xu Yongqing , Tan Hongbo , Zhao Liang
Published: April 2022

Alcohol-induced osteonecrosis of the femoral head (ONFH) is a disabling disease with a high incidence and elusive pathogenesis. Here, we used single-cell RNA sequencing to explore the transcriptomic landscape of mid- and advanced-stage alcohol-induced ONFH. Cells derived from age-matched hip osteoarthritis and femoral neck fracture samples were used as control. Our bioinformatics analysis revealed the disorder of osteogenic-adipogenic differentiation of stromal cells in ONFH and altered regulons such as MEF2C and JUND. In addition, we reported that one of the endothelial cell clusters withACKR1expression exhibited strong chemotaxis and a weak angiogenic ability and expanded with disease progression. Furthermore, ligand-receptor-based cell-cell interaction analysis indicated that ACKR1+ endothelial cells might specifically communicate with stromal cells through the VISFATIN and SELE pathways, thus influencing stromal cell differentiation in ONFH. Overall, our data revealed single cell transcriptome characteristics in alcohol-induced ONFH, which may contribute to the further investigation of ONFH pathogenesis.
A platinum(IV) prodrug strategy to overcome glutathione-based oxaliplatin resistance
Authors: Fronik Philipp , Gutmann Michael , Vician Petra , Stojanovic Mirjana , Kastner Alexander , Heffeter Petra , Pirker Christine , Keppler Bernhard K. , Berger Walter , Kowol Christian R.
Published: April 2022

Clinical efficacy of oxaliplatin is frequently limited by severe adverse effects and therapy resistance. Acquired insensitivity to oxaliplatin is, at least in part, associated with elevated levels of glutathione (GSH). In this study we report on an oxaliplatin-based platinum(IV) prodrug, which releases L-buthionine-S,R-sulfoximine (BSO), an inhibitor of glutamate-cysteine ligase, the rate-limiting enzyme in GSH biosynthesis. Two complexes bearing either acetate (BSO-OxOAc) or an albumin-binding maleimide (BSO-OxMal) as second axial ligand were synthesized and characterized. The in vitro anticancer activity of BSO-OxOAc was massively reduced in comparison to oxaliplatin, proving its prodrug nature. Nevertheless, the markedly lower intracellular oxaliplatin uptake in resistant HCT116/OxR cells was widely overcome by BSO-OxOAc resulting in distinctly reduced resistance levels. Platinum accumulation in organs of a colorectal cancer mouse model revealed higher tumor selectivity of BSO-OxMal as compared to oxaliplatin. This corresponded with increased antitumor activity, resulting in significantly enhanced overall survival. BSO-OxMal-treated tumors exhibited reduced GSH levels, proliferative activity and enhanced DNA damage (pH2AX) compared to oxaliplatin. Conversely, pH2AX staining especially in kidney cells was distinctly increased by oxaliplatin but not by BSO-OxMal. Taken together, our data provide compelling evidence for enhanced tumor specificity of the oxaliplatin(IV)/BSO prodrug.
Directional passive transport of nanodroplets on general axisymmetric surfaces
Authors: Mo Jingwen , Wang Chen , Zeng Jiaying , Sha Jingjie , Li Zhigang , Chen Yunfei
Published: April 2022

An analytical formula of the driving force of nanodroplets on axisymmetric surfaces is developed and validated by MD simulations. A universal theoretical criterion for the onset of directional droplet motion on axisymmetric surfaces is proposed.
Changes in the serum metabolomic profiles of subjects with NAFLD in response to n-3 PUFAs and phytosterol ester: a double-blind randomized controlled trial
Authors: Ding Xinwen , Xu Yinfei , Nie Pan , Zhong Lingyue , Feng Lei , Guan Qi , Song Lihua
Published: April 2022

Co-supplementation of n-3 PUFAs and PSE significantly increased the serum levels of PUFA-containing phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), and some of these metabolites correlated negatively with the degree of hepatic steatosis.
Synthesis of an insulin intercalated graphene oxide nanogel composite: evaluation of its release profile and stability for oral delivery of insulin
Authors: Baloch Shabana Gul , Shaikh Huma , Shah Shahnila , Memon Shahabuddin , Memon Ayaz Ali
Published: April 2022

Graphene oxide based nanogel composite; an efficient oral drug delivery system for sustainable release of insulin.
Thermally activated delayed fluorescence in luminescent cationic copper(i) complexes
Authors: Sandoval-Pauker Christian , Santander-Nelli Mireya , Dreyse Paulina
Published: April 2022

Bibliographic review of cationic Cu(i) complexes that undergo Thermally Activated Delayed Fluorescence (TADF). From the first findings found in the homoleptic and heteroleptic Cu(i)-TADF complexes to the use of this property in lighting devices.
Enzyme assays with supramolecular chemosensors – the label-free approach
Authors: Nilam Mohamed , Hennig Andreas
Published: April 2022

This review comprehensively summarizes the state of the art in label-free supramolecular tandem enzyme assays using supramolecular chemosensors and includes prospective applications in inhibitor screening, optical sensor arrays, and MRI biosensing.
Thioglycolic acid-modified AuNPs as a colorimetric sensor for the rapid determination of the pesticide chlorpyrifos
Authors: Zhang Hongwei , Qu Yuan , Zhang Yanchao , Yan Yumei , Gao Haixiang
Published: April 2022

Herein, we report the preparation of a gold nanoparticle-thioglycolic acid (TGA@AuNP) suspension for the label-free colorimetric detection of the organophosphorus pesticide chlorpyrifos.
Polyoxazoline hydrogels fabricated by stereolithography
Authors: Brossier Thomas , Benkhaled Belkacem Tarek , Colpaert Maxime , Volpi Gael , Guillaume Olivier , Blanquer Sébastien , Lapinte Vincent
Published: April 2022

The development of hydrogel materials in additive manufacturing displaying stiff and strong mechanical properties while maintaining high water uptake remains a great challenge.
Reengineering of cancer cell surface charges can modulate cell migration
Authors: Ghirardello Mattia , Shyam Radhe , Galan M. Carmen
Published: April 2022

Reducing the negative charges induced by the overexpression of cell surface sialic acids using cationic clickable labels leads to a reduction in cancer cell migration without affecting drug supceptibility.
[(Histamine)(18-crown-6)2][BF4]2is a high-temperature piezoelectric
Authors: Li Yi-Rong , Zhang Yun-Fang , Tang Yuan-Yuan , Zhang Han-Yue
Published: April 2022

Host–guest inclusion [(histamine)(18-crown-6)2][BF4]2shows decent piezoelectricity (d33= 5 pC/N) and a high phase transition temperature of 406 K.
Epoxidation vs. dehydrogenation of allylic alcohols: heterogenization of the VO(acac)2 catalyst in a metal–organic framework
Authors: Negro Cristina , Bilanin Cristina , Qu Xiaoni , Oliver-Meseguer Judit , Ferrando-Soria Jesús , Leyva-Pérez Antonio , Armentano Donatella , Pardo Emilio
Published: April 2022

Allylic alcohol epoxidation and dehydrogenation reactivity is distinguished when VO(acac)2 is used in solution or anchored in a metal–organic framework (MOF).
Anion-induced disproportionation of Th(iii) complexes to form Th(ii) and Th(iv) products
Authors: Wedal Justin C. , Cajiao Nathalia , Neidig Michael L. , Evans William J.
Published: April 2022

First example of disproportionation observed for a thorium complex.
Covalent organic frameworks embedded in polystyrene membranes for ion sieving
Authors: Niu Bo , Xin Weiwen , Qian Yongchao , Kong Xiang-Yu , Jiang Lei , Wen Liping
Published: April 2022

A mixed matrix membrane composed of COF-300 and polystyrene (PS) with controllable thickness and porosity achieves ion sieving performance, which is dependent on the regular pore size and surface functional groups of COF-300.
Leveraging algorithmic search in quantum chemical reaction path finding
Authors: Nakao Atsuyuki , Harabuchi Yu , Maeda Satoshi , Tsuda Koji
Published: April 2022

Reaction path finding methods construct a graph connecting reactants and products in a quantum chemical energy landscape. This paper engages in accelerating reaction path finding by introducing the principles of algorithmic search.
N-Doped hollow Fe0.4Co0.6S2@NC nanoboxes derived from a Prussian blue analogue as a sodium ion anode
Authors: Wan Ping , Wang Shijie , Zhu Shuang , Wang Changda , Yu Zhen , Wang Wenjie , Si Yang , Chu Wangsheng , Song Li
Published: April 2022

An N-doped carbon coated hollow nanobox vulcanized from PBA was prepared and applied for a sodium ion battery anode.
In situ preparation of a Co4S3-based electrocatalyst by taking advantage of the controllable components of metal–organic frameworks
Authors: Li Tang-ming , Hu Bing-qian , Han Jing-hua , Lu Wangting , Yu Fan , Li Bao
Published: April 2022

Co4S3 based derivatives had been in situ prepared by utilizing the two-dimensional layered and three-dimensional MOF with the same chemical compositions.
Rethinking the molecular structures of WVIOxsites dispersed on titania: distinct mono-oxo configurations at 430 °C and temperature-dependent transformations
Authors: Kentri Theocharis , Trimpalis Antonios , Misa Adam , Kordouli Eleana , Ramantani Theodora , Boghosian Soghomon
Published: April 2022

The structure of the (WOx)nphase dispersed on TiO2at surface densities of 0.5–4.5 W nm-2was explored byin situRaman and FTIR spectroscopy,18O/16O exchange and Raman spectroscopy in static equilibrium at temperatures of 175–430 °C.
Water soluble organometallic small molecules as promising antibacterial agents: synthesis, physical–chemical properties and biological evaluation to tackle bacterial infections
Authors: Bennour Ines , Ramos M. Núria , Nuez-Martínez Miquel , Xavier Jewel Ann Maria , Buades Ana B. , Sillanpää Reijo , Teixidor Francesc , Choquesillo-Lazarte Duane , Romero Isabel , Martinez-Medina Margarita , Viñas Clara
Published: April 2022

Small anionic metallacarborane molecules with activities down to the nanomolar range against methicillin resistantS. aureus(MRSA) and high selectivity index as promising antimicrobial agents to tackle antibiotic-resistant bacteria.
Modelling nonlocal nonlinear spin dynamics in antiferromagnetic orthoferrites
Authors: Saito Yuichi , Mikhaylovskiy Rostislav V.
Published: April 2022

We calculate nonlinear magnetic dynamics induced by an intense THz pulse in an antiferromagnet. As a result, we reveal an inhomogeneous switching regime involving moving domain walls and propagating magnons.
Non-heme manganese(ii) complex-catalysed oxidative cleavage of 1,2-diols via alcohol-assisted O2 activation
Authors: Huang Zhiliang , Guan Renpeng , Bennett Elliot L. , Xiao Jianliang
Published: April 2022

A well-defined, biologically relevant Mn(ii) complex is found to catalyse the aerobic oxidative cleavage of a wide range of diverse 1,2-diols to afford valuable carbonyl compounds and five-membered heterocycles under irradiation of visible light.
Substrate promiscuities of a bacterial galactokinase and a glucose-1-phosphate uridyltransferase enable xylose salvaging
Authors: Shi Jin-Min , Wu Ting-Ting , Zhou Hui , Zhang Yao-Yao , Liu Li , Widmalm Göran , Voglmeir Josef
Published: April 2022

A bacterial galactokinase (ScGalK) phosphorylates xylose to xylose 1-phosphate, and allows xylose recycling via a simple UDP-xylose 'salvage pathway', which significantly reduces cofactor requirements compared to the known pentose phosphate pathway.
Multifunctional applications for waste zinc–carbon battery to synthesize carbon dots and symmetrical solid-state supercapacitors
Authors: Le Phuoc-Anh , Le Van Qui , Nguyen Nghia Trong , Nguyen Van-Truong , Van Thanh Dang , Phung Thi Viet Bac
Published: April 2022

In this study, we provide a simple and green approach to recycle waste zinc carbon batteries for making carbon dots and porous carbon material.
Insight into the photodegradation mechanism of bisphenol-A by oxygen doped mesoporous carbon nitride under visible light irradiation and DFT calculations
Authors: Shittu Fatimah Bukola , Iqbal Anwar , Ahmad Mohammad Norazmi , Yusop Muhammad Rahimi , Ibrahim Mohamad Nasir Mohamad , Sabar Sumiyyah , Wilson Lee D. , Yanto Dede Heri Yuli
Published: April 2022

Glucose is an excellent oxygen atoms donor for synthesising oxygen doped mesoporous carbon nitride (O-MCN). The oxygen doping created sub-gap impurity, preserved surface area and created broad pore size distribution to enhance the photodegradation of bisphenol A (BPA).
A review of hetero-structured Ni-based active catalysts for urea electrolysis
Authors: Li Jiaxin , Wang Shuli , Sun Sijia , Wu Xiang , Zhang Baogang , Feng Ligang
Published: April 2022

Hetero-structured Ni-based active catalysts for urea electrolysis were reviewed, and challenges were faced for the integration of the components to fully make use of their strengths and make up for each other's weaknesses.
Ion transport through layered hydrogels for low-frequency energy harvesting toward self-powered chemical systems
Authors: Biutty Merreta Noorenza , Koo Ja-Min , Kim Joo Hyun , Kim Seonho , Choi U. Hyeok , Imani Kusuma Betha Cahaya , Yoon Jinhwan , Chang Byoung-Yong , Yoo Seong Il
Published: April 2022

Stress-induced ion transport through three-layered hydrogels with different stiffnesses and ion selectivities enabled the efficient conversion of low-frequency mechanical vibrations into electricity.
Rational engineering of biomimetic flavylium fluorophores for regulating the lysosomal and mitochondrial localization behavior by pH-induced structure switch and application to fluorescence imaging
Authors: Wang Liping , He Mengye , Sun Yu , Liu Li , Ye Yuan , Liu Lingrong , Shen Xing-Can , Chen Hua
Published: April 2022

Versatile and straightforward methods for precisely regulating the lysosomal and mitochondrial localization behavior of biomimetic fluorophores are highly desirable.
Lewis acid–base pair doping of p-type organic semiconductors
Authors: Peterson Kelly A. , Chabinyc Michael L.
Published: April 2022

Lewis acid–base pairs can be used as p-type dopants for semiconducting polymers. This co-doping process greatly enhances the doping efficiency of B(C6F5)3 and leads to high conductivity in solution processed films of regioregular P3HT.