bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrative Messages and the Use of Emotional Appeals on Endometriosis Screening Intention: The Mediating Role of Positive Affect
Authors: Worsdale Allison , Liu Jiaying
Published: June 2023

Endometriosis affects around 10% of women globally, yet the awareness and screening rates for this condition are relatively low. Utilizing an online survey-based experiment with a sample of 18–30-year-old young women (N = 326), this study aimed to investigate the efficacy of narrative messages vs. non-narrative messages for promoting endometriosis screening intention, as well as to evaluate the effectiveness of hope appeal vs. fear appeal in narrative messages. The study also examined the potential mediating mechanisms through self-efficacy and positive affect responses that may help elucidate the effect of emotional appeals on behavioral intentions, while taking into account an individual’s readiness to change. Findings indicated that narrative and non-narrative messages did not produce significantly different screening intentions. Compared to the use of fear appeal, the hope appeal in narrative messages predicted a higher level of positive affect responses, which was associated with increased endometriosis screening intentions. Individual difference in readiness to engage in endometriosis screening was not found to be a significant moderator. These results have implications for future research utilizing hope appeals in narrative health messaging. The observed significant mediational pathway through positive affect advances understanding of positive discrete emotions as facilitators to health-related cognition and behavior changes.
Advancing Research: An Examination of Differences in Characteristics of Sexual and Non-Sexual Offense Recidivism Using a 10-Year Follow-Up
Authors: Zgoba Kristen M. , Liu Lin , Matthews Dylan T.
Published: June 2023

In this article, we examine our current understanding of adverse childhood experiences (ACEs) and the intersection of mental health challenges and substance use on sexual and non-sexual recidivism. This study uses administrative data and comprehensive case files of a sample of 626 individuals who were incarcerated for a sexual offense. Each case was standardized to a 10-year post-release follow-up time for criminal history review. Findings reveal that ACEs, mental health challenges, and substance use disorder, along with a variety of other factors, affect the pathway to re-offending differently. Interestingly, despite the recent legislative push to utilize one standardized predictor of risk, individuals who commit sexual offenses (ICSOs) had very different re-offending patterns based on historic life events. This research will inform the current legislative debate by providing relevant empirical data on a large sample of ICSOs followed for a substantial period of time.
The Impact of the No Jab No Play and No Jab No Pay Legislation in Australia: A Scoping Review
Authors: Burns Sharyn , Bhoyroo Ranila , Leavy Justine E. , Portsmouth Linda , Millar Lynne , Jancey Jonine , Hendriks Jacqueline , Saltis Hanna , Tohotoa Jenny , Pollard Christina
Published: June 2023

Australia has a long history of population-based immunisation programs including legislations. This paper reports on a review of evaluations of the impact of the federal No Jab No Pay (NJNPay) and state implemented No Jab No Play (NJNPlay) legislations on childhood immunisation coverage and related parental attitudes. Five databases were searched for peer-review papers (Medline (Ovid); Scopus; PsycInfo; ProQuest; and CINAHL). Additional searches were conducted in Google Scholar and Informit (Australian databases) for grey literature. Studies were included if they evaluated the impact of the Australian NJNPay and/or NJNPlay legislations. Ten evaluations were included: nine peer-review studies and one government report. Two studies specifically evaluated NJNPlay, five evaluated NJNPay, and three evaluated both legislations. Findings show small but gradual and significant increases in full coverage and increases in catch-up vaccination after the implementation of the legislations. Full coverage was lowest for lower and higher socio-economic groups. Mandates are influential in encouraging vaccination; however, inequities may exist for lower income families who are reliant on financial incentives and the need to enrol their children in early childhood centres. Vaccine refusal and hesitancy was more evident among higher income parents while practical barriers were more likely to impact lower income families. Interventions to address access and vaccine hesitancy will support these legislations.
Is Smart Working Beneficial for Workers’ Wellbeing? A Longitudinal Investigation of Smart Working, Workload, and Hair Cortisol/Dehydroepiandrosterone Sulfate during the COVID-19 Pandemic
Authors: Falco Alessandra , Girardi Damiano , Elfering Achim , Peric Tanja , Pividori Isabella , Dal Corso Laura
Published: June 2023

Building on the job demands–resources (JD-R) and allostatic load (AL) models, in the present study we examined the role of smart working (SW) in the longitudinal association between workload/job autonomy (JA) and a possible biomarker of work-related stress (WRS) in the hair—namely, the cortisol–dehydroepiandrosterone sulfate (DHEA(S)) ratio—during the COVID-19 pandemic. Overall, 124 workers completed a self-report questionnaire (i.e., psychological data) at Time 1 (T1) and provided a strand of hair (i.e., biological data) three months later (Time 2, T2). Results from moderated multiple regression analysis showed that SW at T1 was negatively associated with the hair cortisol/DHEA(S) ratio at T2. Additionally, the interaction between workload and SW was significant, with workload at T1 being positively associated with the hair cortisol/DHEA(S) ratio at T2 among smart workers. Overall, this study indicates that SW is a double-edged sword, with both positive and negative consequences on employee wellbeing. Furthermore, our findings suggest that the hair cortisol/DHEA(S) ratio is a promising biomarker of WRS. Practical implications that organizations and practitioners can adopt to prevent WRS and promote organizational wellbeing are discussed.
Best Practices for Notification of Unexpected, Violent, and Traumatic Death: A Scoping Review
Authors: De Leo Diego , Zammarrelli Josephine , Marinato Giulia , Capelli Marta , Viecelli Giannotti Andrea
Published: June 2023

Background: Death reporting is a delicate task. The ways in which it is carried out can have a significant impact on both the recipient and the notifier, especially in the event of a sudden, violent, and traumatic death. Empathetic, sensitive, and attentive communication with survivors can represent a first opportunity to support the bereavement process. The acquisition of specific skills for the delivery of the death notification is necessary for the professional who carries out the communication to increase self-efficacy, knowledge, and perception of competence in this area. Objective: To map what the literature has produced on the theme of best practices for the notification of unexpected, violent, and traumatic deaths and to provide guidance for the formulation of appropriate best practices and the development of effective educational programs. Methods: A review was conducted using the PRISMA Scoping Review extension on English language literature published between 1966 and 2022. Results: Starting from the initial 3781 titles, 67 articles were selected. From a thematic point of view, the analysis of the contents made it possible to identify five dimensions: (1) general guidelines in relation to various professional figures; (2) specific protocols; (3) guidelines for notifying death to children; (4) guidelines for notification of death by telephone; and (5) recommendations and suggestions for death notification training programs. Discussion: Death notification is configured as a process, divided into sequential phases. The act of notification constitutes the central phase during which communication is carried out. The communication of death is context-specific; therefore, it should require the creation of specific protocols for the various professions involved in the task, along with targeted theoretical and practical training. Conclusions: The importance of defining specific guidelines for the various professionals and standardized programs of theoretical and practical training emerges. The implementation of future sectoral studies will allow evaluations of the effectiveness of these protocols and programs.
Degradation of a New Herbicide Florpyrauxifen-Benzyl in Water: Kinetics, Various Influencing Factors and Its Reaction Mechanisms
Authors: Zhou Rendan , Dong Zemin , Wang Long , Zhou Wenwen , Zhao Weina , Wu Tianqi , Chang Hailong , Lin Wei , Li Baotong
Published: June 2023

Florpyrauxifen-benzyl is a novel herbicide used to control weeds in paddy fields. To clarify and evaluate its hydrolytic behavior and safety in water environments, its hydrolytic characteristics were investigated under varying temperatures, pH values, initial mass concentrations and water types, as well as the effects of 40 environmental factors such as microplastics (MPs) and disposable face masks (DFMs). Meanwhile, hydrolytic products were identified by UPLC-QTOF-MS/MS, and its hydrolytic pathways were proposed. The effects of MPs and DFMs on hydrolytic products and pathways were also investigated. The results showed that hydrolysis of florpyrauxifen-benzyl was a spontaneous process driven by endothermic, base catalysis and activation entropy increase and conformed to the first-order kinetics. The temperature had an obvious effect on hydrolysis rate under alkaline condition, the hydrolysis reaction conformed to Arrhenius formula, and activation enthalpy, activation entropy, and Gibbs free energy were negatively correlated with temperature. Most of environmental factors promoted hydrolysis of florpyrauxifen-benzyl, especially the cetyltrimethyl ammonium bromide (CTAB). The hydrolysis mechanism was ester hydrolysis reaction with a main product of florpyrauxifen. The MPs and DFMs did not affect the hydrolytic mechanisms but the hydrolysis rate. The results are crucial for illustrating and assessing the environmental fate and risks of florpyrauxifen-benzyl.
Extending AAV Packaging Cargo through Dual Co-Transduction: Efficient Protein Trans-Splicing at Low Vector Doses
Authors: Ferreira Mariana V. , Fernandes Sofia , Almeida Ana Isabel , Neto Salomé , Mendes João P. , Silva Ricardo J. S. , Peixoto Cristina , Coroadinha Ana Sofia
Published: June 2023

Adeno-associated viral (AAV) vectors represent one of the leading platforms for gene delivery. Nevertheless, their small packaging capacity restricts their use for diseases requiring large-gene delivery. To overcome this, dual-AAV vector systems that rely on protein trans-splicing were developed, with the split-intein Npu DnaE among the most-used. However, the reconstitution efficiency of Npu DnaE is still insufficient, requiring higher vector doses. In this work, two split-inteins, Cfa and Gp41-1, with reportedly superior trans-splicing were evaluated in comparison with Npu DnaE by transient transfections and dual-AAV in vitro co-transductions. Both Cfa and Gp41-1 split-inteins enabled reconstitution rates that were over two-fold higher than Npu DnaE and 100% of protein reconstitution. The impact of different vector preparation qualities in split-intein performances was also evaluated in co-transduction assays. Higher-quality preparations increased split-inteins’ performances by three-fold when compared to low-quality preparations (60–75% vs. 20–30% full particles, respectively). Low-quality vector preparations were observed to limit split-gene reconstitutions by inhibiting co-transduction. We show that combining superior split-inteins with higher-quality vector preparations allowed vector doses to be decreased while maintaining high trans-splicing rates. These results show the potential of more-efficient protein-trans-splicing strategies in dual-AAV vector co-transduction, allowing the extension of its use to the delivery of larger therapeutic genes.
Collective Domain Motion Facilitates Water Transport in SGLT1
Authors: Sever Marko , Merzel Franci
Published: June 2023

The human sodium–glucose cotransporter protein (SGLT1) is an important representative of the sodium solute symporters belonging to the secondary active transporters that are critical to the homeostasis of sugar, sodium, and water in the cell. The underlying transport mechanism of SGLT1 is based on switching between inward- and outward-facing conformations, known as the alternating access model, which is crucial for substrate transport, and has also been postulated for water permeation. However, the nature of water transport remains unclear and is disputed along the passive and active transport, with the latter postulating the presence of the pumping effect. To better examine the water transport in SGLT1, we performed a series of equilibrium all-atom molecular dynamics simulations, totaling over 6 μs of sample representative conformational states of SGLT1 and its complexes, with the natural substrates, ions, and inhibitors. In addition to elucidating the basic physical factors influencing water permeation, such as channel openings and energetics, we focus on dynamic flexibility and its relationship with domain motion. Our results clearly demonstrate a dependence of instantaneous water flux on the channel opening and local water diffusion in the channel, strongly supporting the existence of a passive water transport in SGLT1. In addition, a strong correlation found between the local water diffusion and protein domain motion, resembling the “rocking-bundle” motion, reveals its facilitating role in the water transport.
Secretogranin III Selectively Promotes Vascular Leakage in the Deep Vascular Plexus of Diabetic Retinopathy
Authors: Ji Liyang , Waduge Prabuddha , Wu Yan , Huang Chengchi , Kaur Avinash , Oliveira Paola , Tian Hong , Zhang Jinsong , Stout J. Timothy , Weng Christina Y. , Webster Keith A. , Li Wei
Published: June 2023

Diabetic retinopathy (DR), a leading cause of vision loss in working-age adults, induces mosaic patterns of vasculopathy that may be associated with spatial heterogeneity of intraretinal endothelial cells. We recently reported that secretogranin III (Scg3), a neuron-derived angiogenic and vascular leakage factor, selectively binds retinal vessels of diabetic but not healthy mice. Here, we investigated endothelial heterogeneity of three retinal vascular plexuses in DR pathogenesis and the therapeutic implications. Our unique in vivo ligand binding assay detected a 22.7-fold increase in Scg3 binding to retinal vessels of diabetic mice relative to healthy mice. Functional immunohistochemistry revealed that Scg3 predominantly binds to the DR-stressed CD31− deep retinal vascular plexus but not to the relatively healthy CD31+ superficial and intermediate plexuses within the same diabetic retina. In contrast, VEGF bound to healthy and diabetic retinal vessels indiscriminately with low activity. FITC-dextran assays indicated that selectively increased retinal vascular leakage coincides with Scg3 binding in diabetic mice that was independent of VEGF, whereas VEGF-induced leakage did not distinguish between diabetic and healthy mice. Dose–response curves showed that the anti-Scg3 humanized antibody (hAb) and anti-VEGF aflibercept alleviated DR leakage with equivalent efficacies, and that the combination acted synergistically. These findings suggest: (i) the deep plexus is highly sensitive to DR; (ii) Scg3 binding to the DR deep plexus coincides with the loss of CD31 and compromised endothelial junctions; (iii) anti-Scg3 hAb alleviates vascular leakage by selectively targeting the DR-stressed deep plexus within the same diabetic retina; (iv) combined anti-Scg3 and anti-VEGF treatments synergistically ameliorate DR through distinct mechanisms.
The Role of Subretinal Injection in Ophthalmic Surgery: Therapeutic Agent Delivery and Other Indications
Authors: Tripepi Domenico , Jalil Assad , Ally Naseer , Buzzi Matilde , Moussa George , Rothschild Pierre-Raphaël , Rossi Tommaso , Ferrara Mariantonia , Romano Mario R.
Published: June 2023

Subretinal injection is performed in vitreoretinal surgery with two main aims, namely, the subretinal delivery of therapeutic agents and subretinal injection of fluid to induce a controlled and localized macular detachment. The growing interest in this technique is mainly related to its suitability to deliver gene therapy in direct contact with target tissues. However, subretinal injection has been also used for the surgical management of submacular hemorrhage through the subretinal delivery of tissue plasminogen activator, and for the repair of full-thickness macular holes, in particular refractory ones. In the light of the increasing importance of this maneuver in vitreoretinal surgery as well as of the lack of a standardized surgical approach, we conducted a comprehensive overview on the current indications for subretinal injection, surgical technique with the available variations, and the potential complications.
It Takes Two to Tango! Protein–Protein Interactions behind cAMP-Mediated CFTR Regulation
Authors: Murabito Alessandra , Bhatt Janki , Ghigo Alessandra
Published: June 2023

Over the last fifteen years, with the approval of the first molecular treatments, a breakthrough era has begun for patients with cystic fibrosis (CF), the rare genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These molecules, known as CFTR modulators, have led to unprecedented improvements in the lung function and quality of life of most CF patients. However, the efficacy of these drugs is still suboptimal, and the clinical response is highly variable even among individuals bearing the same mutation. Furthermore, not all patients carrying rare CFTR mutations are eligible for CFTR modulator therapies, indicating the need for alternative and/or add-on therapeutic approaches. Because the second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) represents the primary trigger for CFTR activation and a major regulator of different steps of the life cycle of the channel, there is growing interest in devising ways to fine-tune the cAMP signaling pathway for therapeutic purposes. This review article summarizes current knowledge regarding the role of cAMP signalosomes, i.e., multiprotein complexes bringing together key enzymes of the cAMP pathway, in the regulation of CFTR function, and discusses how modulating this signaling cascade could be leveraged for therapeutic intervention in CF.
ABCG2 Gene and ABCG2 Protein Expression in Colorectal Cancer—In Silico and Wet Analysis
Authors: Sałagacka-Kubiak Aleksandra , Zawada Dawid , Saed Lias , Kordek Radzisław , Jeleń Agnieszka , Balcerczak Ewa
Published: June 2023

ABCG2 (ATP-binding cassette superfamily G member 2) is a cell membrane pump encoded by the ABCG2 gene. ABCG2 can protect cells against compounds initiating and/or intensifying neoplasia and is considered a marker of stem cells responsible for cancer growth, drug resistance and recurrence. Expression of the ABCG2 gene or its protein has been shown to be a negative prognostic factor in various malignancies. However, its prognostic significance in colorectal cancer remains unclear. Using publicly available data, ABCG2 was shown to be underexpressed in colon and rectum adenocarcinomas, with lower expression compared to both the adjacent nonmalignant lung tissues and non-tumour lung tissues of healthy individuals. This downregulation could result from the methylation level of some sites of the ABCG2 gene. This was connected with microsatellite instability, weight and age among patients with colon adenocarcinoma, and with tumour localization, population type and age of patients for rectum adenocarcinoma. No association was found between ABCG2 expression level and survival of colorectal cancer patients. In wet analysis of colorectal cancer samples, neither ABCG2 gene expression, analysed by RT-PCR, nor ABCG2 protein level, assessed by immunohistochemistry, was associated with any clinicopathological factors or overall survival. An ABCG2-centered protein–protein interaction network build by STRING showed proteins were found to be involved in leukotriene, organic anion and xenobiotic transport, endodermal cell fate specification, and histone methylation and ubiquitination. Hence, ABCG2 underexpression could be an indicator of the activity of certain signalling pathways or protein interactors essential for colorectal carcinogenesis.
Chitosan-Based Biomaterials for Hemostatic Applications: A Review of Recent Advances
Authors: Gheorghiță Daniela , Moldovan Horațiu , Robu Alina , Bița Ana-Iulia , Grosu Elena , Antoniac Aurora , Corneschi Iuliana , Antoniac Iulian , Bodog Alin Dănuț , Băcilă Ciprian Ionuț
Published: June 2023

Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures the immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing a novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as antibacterial, antifungal, hemostatic, and analgesic activity in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic biomaterials and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years.
Protein Tyrosine Phosphatase Non-Receptor 11 (PTPN11/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC)
Authors: Richards Cathy E. , Elamin Yasir Y. , Carr Aoife , Gately Kathy , Rafee Shereen , Cremona Mattia , Hanrahan Emer , Smyth Robert , Ryan Daniel , Morgan Ross K. , Kennedy Susan , Hudson Lance , Fay Joanna , O’Byrne Kenneth , Hennessy Bryan T. , Toomey Sinead
Published: June 2023

PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated PTPN11 in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)). Further, PTPN11 mutation cases were identified in additional cohorts, including TCGA, Broad, and MD Anderson datasets and the COSMIC database. PTPN11 constructs harbouring PTPN11 E76A, A72D and C459S mutations were stably expressed in IL-3 dependent BaF3 cells and NSCLC cell lines (NCI-H1703, NCI-H157, NCI-H1299). The MAPK and PI3K pathway activation was evaluated using Western blotting. PTPN11/Shp2 phosphatase activity was measured in whole-cell protein lysates using an Shp2 assay kit. The Shp2 inhibitor (SHPi) was assessed both in vitro and in vivo in a PTPN11-mutated cell line for improved responses to MAPK and PI3K targeting therapies. Somatic PTPN11 hotspot mutations occurred in 4/98 (4.1%) adenocarcinomas and 7/258 (2.7%) squamous cells of 356 NSCLC patients. Additional 26 PTPN11 hotspot mutations occurred in 23 and 3 adenocarcinomas and squamous cell carcinoma, respectively, across the additional cohorts. Mutant PTPN11 significantly increased the IL-3 independent survival of Ba/F3 cells compared to wildtype PTPN11 (p < 0.0001). Ba/F3, NCI-H1703, and NCI-H157 cells expressing mutant PTPN11 exhibited increased PTPN11/Shp2 phosphatase activity and phospho-ERK1/2 levels compared to cells expressing wildtype PTPN11. The transduction of the PTPN11 inactivating mutation C459S into NSCLC cell lines led to decreased phospho-ERK, as well as decreased phospho-AKT in the PTPN11-mutated NCI-H661 cell line. NCI-H661 cells (PTPN11-mutated, KRAS-wild type) were significantly more sensitive to growth inhibition by the PI3K inhibitor copanlisib (IC50: 13.9 ± 4.7 nM) compared to NCI-H1703 (PTPN11/KRAS-wild type) cells (IC50: >10,000 nM). The SHP2 inhibitor, in combination with the PI3K targeting therapy copanlisib, showed no significant difference in tumour development in vivo; however, this significantly prevented MAPK pathway induction in vitro (p < 0.0001). PTPN11/Shp2 demonstrated the in vitro features of a driver oncogene and could potentially sensitize NSCLC cells to PI3K inhibition and inhibit MAPK pathway activation following PI3K pathway targeting.
Immunotherapeutic Approaches for the Treatment of Glioblastoma Multiforme: Mechanism and Clinical Applications
Authors: Das Suprava , Dash Banendu Sunder , Premji Thejas P. , Chen Jyh-Ping
Published: June 2023

Glioma is one of the most aggressive types of primary brain tumor with a high-grade glioma known as glioblastoma multiforme (GBM). Patients diagnosed with GBM usually have an overall survival rate of less than 18 months after conventional therapy. This bleak prognosis underlines the need to consider new therapeutic interventions for GBM treatment to overcome current treatment limitations. By highlighting different immunotherapeutic approaches currently in preclinical and clinical trials, including immune checkpoint inhibitors, chimeric antigen receptors T cells, natural killer cells, vaccines, and combination therapy, this review aims to discuss the mechanisms, benefits, and limitations of immunotherapy in treating GBM patients.
Irisin Is Target of Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor-Mediated Signaling in Skeletal Muscle Cells
Authors: Pierucci Federica , Chirco Antony , Meacci Elisabetta
Published: June 2023

Irisin is a hormone-like myokine produced in abundance by skeletal muscle (SkM) in response to exercise. This myokine, identical in humans and mice, is involved in many signaling pathways related to metabolic processes. Despite much evidence on the regulators of irisin and the relevance of sphingolipids for SkM cell biology, the contribution of these latter bioactive lipids to the modulation of the myokine in SkM is missing. In particular, we have examined the potential involvement in irisin formation/release of sphingosine-1-phosphate (S1P), an interesting bioactive molecule able to act as an intracellular lipid mediator as well as a ligand of specific G-protein-coupled receptors (S1PR). We demonstrate the existence of distinct intracellular pools of S1P able to affect the expression of the irisin precursor FNDC. In addition, we establish the crucial role of the S1P/S1PR axis in irisin formation/release as well as the autocrine/paracrine effects of irisin on myoblast proliferation and myogenic differentiation. Altogether, these findings provide the first evidence for a functional crosstalk between the S1P/S1PR axis and irisin signaling, which may open new windows for potential therapeutic treatment of SkM dysfunctions.
Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies
Authors: Stephan-Falkenau Susann , Streubel Anna , Mairinger Thomas , Blum Torsten-Gerriet , Kollmeier Jens , Mairinger Fabian D. , Bauer Torsten , Pfannschmidt Joachim , Hollmann Manuel , Wessolly Michael
Published: June 2023

Pulmonary sarcomatoid carcinoma (PSC) has highly aggressive biological behaviour and poor clinical outcomes, raising expectations for new therapeutic strategies. We characterized 179 PSC by immunohistochemistry, next-generation sequencing and in silico analysis using a deep learning algorithm with respect to clinical, immunological and molecular features. PSC was more common in men, older ages and smokers. Surgery was an independent factor (p < 0.01) of overall survival (OS). PD-L1 expression was detected in 82.1% of all patients. PSC patients displaying altered epitopes due to processing mutations showed another PD-L1-independent immune escape mechanism, which also significantly influenced OS (p < 0.02). The effect was also maintained when only advanced tumour stages were considered (p < 0.01). These patients also showed improved survival with a significant correlation for immunotherapy (p < 0.05) when few or no processing mutations were detected, although this should be interpreted with caution due to the small number of patients studied. Genomic alterations for which there are already approved drugs were present in 35.4% of patients. Met exon 14 skipping was found more frequently (13.7%) and EGFR mutations less frequently (1.7%) than in other NSCLC. In summary, in addition to the divergent genomic landscape of PSC, the specific immunological features of this prognostically poor subtype should be considered in therapy stratification.
Exploring the Mitogenomes of Mantodea: New Insights from Structural Diversity and Higher-Level Phylogenomic Analyses
Authors: Liu Qinpeng , Liu Yingqi , Liu Qiaoqiao , Tian Li , Li Hu , Song Fan , Cai Wanzhi
Published: June 2023

The recently reorganized classification of Mantodea has made significant progress in resolving past homoplasy problems, although some relationships among higher taxa remain uncertain. In the present study, we utilized newly sequenced mitogenomes and nuclear gene sequences of 23 mantid species, along with published data of 53 mantises, to perform familial-sampling structural comparisons of mantodean mitogenomes and phylogenomic studies. Our rstructural analysis revealed generally conserved mitogenome organizations, with a few cases of tRNA gene rearrangements, including the detection of trnL2 duplication for the first time. In our phylogenetic analysis, we found a high degree of compositional heterogeneity and lineage-specific evolutionary rates among mantodean mitogenomes, which frequently corresponded to several unexpected groupings in the topologies under site-homogeneous models. In contrast, the topologies obtained using the site-heterogeneous mixture model fit the currently accepted phylogeny of Mantodea better. Topology tests and four-cluster likelihood mapping analyses further determined the preferred topologies. Our phylogenetic results confirm the monophyly of superfamilial groups Schizomantodea, Amerimantodea, Heteromantodea, Promantidea, and Mantidea and recover the early-branching relationships as (Mantoidoidea + (Amerimantodea + (Metallyticoidea + Cernomantodea))). Additionally, the results suggest that the long-unresolved phylogenetic position of Majangidae should be placed within Mantidea, close to Mantoidea, rather than within Epaphroditoidea. Our findings contribute to understanding the compositional and structural diversity in mantodean mitogenomes, underscore the importance of evolutionary model selection in phylogenomic studies, and provide new insights into the high-level phylogeny of Mantodea.
Metabolic Biomarkers Differentiate a Surgical Intervertebral Disc from a Nonsurgical Intervertebral Disc
Authors: Toczylowska Beata , Woznica Michal , Zieminska Elzbieta , Krolicki Leszek
Published: June 2023

Background: Degeneration of the intervertebral disc (IVD) is caused by disturbances in metabolic processes, which lead to structural disorders. The aim of this report is to analyze metabolic disorders in the degeneration process by comparing control discs with degenerated discs. In our research on the nucleus pulposus (NP), we used NMR spectroscopy of extracts of hydrophilic and hydrophobic compounds of the tissue. Methods: Nuclear magnetic resonance (NMR) spectroscopy allows the study of biochemistry and cellular metabolism in vitro. Hydrophilic and hydrophobic compounds were extracted from the NP of the intervertebral disc. In the NMR spectra, metabolites were identified and quantitatively analyzed. The results of our research indicate disturbances in the biosynthesis and metabolism of cholesterol, the biosynthesis and degradation of various fatty acid groups, ketone bodies, or lysine, and the metabolism of glycerophospholipids, purines, glycine, inositol, galactose, alanine, glutamate, and pyruvate in the biosynthesis of valine and isoleucine, leucine. All these disorders indicate pathomechanisms related to oxidative stress, energy, neurotransmission disturbances, and disturbances in the structure and functioning of cell membranes, inflammation, or chronic pain generators. Conclusions: NMR spectroscopy allows the identification of metabolites differentiating surgical from nonsurgical discs. These data may provide guidance in in vivo MRS studies in assessing the severity of lesions of the disc.
The Effect of GLUT1 and HIF-1α Expressions on Glucose Uptake and Patient Survival in Non-Small-Cell Lung Carcinoma
Authors: Kokeza Josipa , Strikic Ante , Ogorevc Marin , Kelam Nela , Vukoja Martina , Dilber Ivo , Zekic Tomas Sandra
Published: June 2023

Lung cancer is the second-most-common cancer while being the leading cause of cancer deaths worldwide. It has been found that glucose transporter 1 (GLUT1) and hypoxia-inducible factor 1α (HIF-1α) are overexpressed in various malignancies and that they correlate with the maximum standard uptake values (SUVmax) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) and poor prognosis. In this study, we aim to evaluate the relationship between the SUVmax, GLUT1, and HIF-1α expression with primary tumor size, histological type, lymph node metastases, and patient survival. Of the 48 patients with non-small-cell lung cancer, those with squamous cell carcinomas (SCCs) had significantly higher GLUT1 and HIF-1α immunohistochemical expressions in comparison to adenocarcinomas (ACs), while there was no statistically significant difference in FDG accumulation between them. No significant correlation was noted between either GLUT1 or HIF-1α protein expression and FDG uptake and overall survival. However, an analysis of tumor transcriptomics showed a significant difference in overall survival depending on mRNA expression; patients with SCC and high HIF-1α levels survived longer compared to those with low HIF-1α levels, while patients with AC and low GLUT1 levels had a higher average survival time than those with high GLUT1 levels. Further studies are needed to determine the prognostic value of the expression of these factors depending on the histologic type.
Effect of Silicon on Micronutrient Content in New Potato Tubers
Authors: Wadas Wanda , Kondraciuk Tomasz
Published: June 2023

Since silicon can improve nutrient uptake in plants, the effect of foliar silicon (sodium metasilicate) application on micronutrient content in early crop potato tuber was investigated. Silicon was applied at dosages of 23.25 g Si∙ha–1 or 46.50 g Si∙ha–1 (0.25 L∙ha–1 or 0.50 L∙ha–1 of Optysil) once at the leaf development stage (BBCH 14–16), or at the tuber initiation stage (BBCH 40–1), and twice, at the leaf development and tuber initiation stages. Potatoes were harvested 75 days after planting (the end of June). Foliar-applied silicon reduced the Fe concentration and increased Cu and Mn concentrations in early crop potato tubers under water deficit conditions but did not affect the Zn, B, or Si concentrations. The dosage and time of silicon application slightly affected the Fe and Cu concentration in the tubers. Under drought conditions, the highest Mn content in the tuber was observed when 46.50 g Si∙ha–1 was applied at the leaf development stage, whereas under periodic water deficits, it was highest with the application of the same silicon dosage at the tuber initiation stage (BBCH 40–41). The Si content in tubers was negatively correlated with the Fe and B content, and positively correlated with the Cu and Mn content.
Direct Effects of Toxic Divalent Cations on Contractile Proteins with Implications for the Heart: Unraveling Mechanisms of Dysfunction
Authors: Gerzen Oksana P. , Votinova Veronika O. , Potoskueva Iulia K. , Tzybina Alyona E. , Nikitina Larisa V.
Published: June 2023

The binding of calcium and magnesium ions to proteins is crucial for regulating heart contraction. However, other divalent cations, including xenobiotics, can accumulate in the myocardium and enter cardiomyocytes, where they can bind to proteins. In this article, we summarized the impact of these cations on myosin ATPase activity and EF-hand proteins, with special attention given to toxic cations. Optimal binding to EF-hand proteins occurs at an ionic radius close to that of Mg2+ and Ca2+. In skeletal Troponin C, Cd2+, Sr2+, Pb2+, Mn2+, Co2+, Ni2+, Ba2+, Mg2+, Zn2+, and trivalent lanthanides can substitute for Ca2+. As myosin ATPase is not a specific MgATPase, Ca2+, Fe2+, Mn2+, Ni2+, and Sr2+ could support myosin ATPase activity. On the other hand, Zn2+ and Cu2 significantly inhibit ATPase activity. The affinity to various divalent cations depends on certain proteins or their isoforms and can alter with amino acid substitution and post-translational modification. Cardiac EF-hand proteins and the myosin ATP-binding pocket are potential molecular targets for toxic cations, which could significantly alter the mechanical characteristics of the heart muscle at the molecular level.
Phage Targeting Neonatal Meningitis E. coli K1 In Vitro in the Intestinal Microbiota of Pregnant Donors and Impact on Bacterial Populations
Authors: Antoine Céline , Laforêt Fanny , Goya-Jorge Elizabeth , Gonza Irma , Lebrun Sarah , Douny Caroline , Duprez Jean-Noël , Fall Abdoulaye , Taminiau Bernard , Scippo Marie-Louise , Daube Georges , Thiry Damien , Delcenserie Véronique
Published: June 2023

Escherichia coli K1 is a leading cause of neonatal meningitis. The asymptomatic carriage of these strains in the maternal intestinal microbiota constitutes a risk of vertical transmission to the infant at birth. The aim of this work was to evaluate the efficacy of phage therapy against E. coli K1 in an intestinal environment and its impact on the intestinal microbiota. For this purpose, three independent experiments were conducted on the SHIME® system, the first one with only the phage vB_EcoP_K1_ULINTec4, the second experiment with only E. coli K1 and the last experiment with both E. coli K1 and the phage. Microbiota monitoring was performed using metagenetics, qPCR, SCFA analysis and the induction of AhR. The results showed that phage vB_EcoP_K1_ULINTec4, inoculated alone, was progressively cleared by the system and replicates in the presence of its host. E. coli K1 persisted in the microbiota but decreased in the presence of the phage. The impact on the microbiota was revealed to be donor dependent, and the bacterial populations were not dramatically affected by vB_K1_ULINTec4, either alone or with its host. In conclusion, these experiments showed that the phage was able to infect the E. coli K1 in the system but did not completely eliminate the bacterial load.
Pentoxifylline Inhibits TNF-α/TGF-β1-Induced Epithelial-Mesenchymal Transition via Suppressing the NF-κB Pathway and SERPINE1 Expression in CaSki Cells
Authors: Palafox-Mariscal Luis Arturo , Ortiz-Lazareno Pablo Cesar , Jave-Suárez Luis Felipe , Aguilar-Lemarroy Adriana , Villaseñor-García María Martha , Cruz-Lozano José Roberto , González-Martínez Karen Lilith , Méndez-Clemente Aníbal Samael , Bravo-Cuellar Alejandro , Hernández-Flores Georgina
Published: June 2023

Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant organs (metastasis). The epithelial-mesenchymal transition (EMT) is a fundamental process of cancer metastasis. Inflammation can lead to tumor progression, EMT induction, and metastasis. The inflammatory microenvironment is a potent inducer of EMT; inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Transforming growth factor-beta (TGF-β1) activate transcriptional factors such as STAT3, Snail, Smad, and the Nuclear Factor kappa light-chain-enhancer of activated beta cells (NF-κΒ), which drive EMT. Anti-inflammatory compounds may be an option in the disruption of EMT. PenToXifylline (PTX) possesses potent anti-inflammatory effects by inhibiting NF-κB activity. In addition, PTX exerts an anti-fibrotic effect by decreasing Smad2/3/4. We hypothesize that PTX could exert anti-EMT effects. CaSki human cervical tumor cells were exposed to TNF-α 10 ng/mL and TGF-β1 alone or in combination for 5 days. Our results revealed that TNF-α and TGF-β1 induced N-cadherin and Vimentin, confirming the induction of EMT. Furthermore, the combination of cytokines synergized the expression of mesenchymal proteins, enhanced IκBα and p65 phosphorylation, and upregulated Serpin family E member 1 (SERPINE1) mRNA. PTX pretreatment prior to the addition of TNF-α and TGF-β1 significantly reduced N-cadherin and Vimentin levels. To our knowledge, this is the first time that this effect of PTX has been reported. Additionally, PTX reduced the phosphorylation of IκB-α and p65 and significantly decreased SERPINE1 expression, cell proliferation, migration, and invasion. In conclusion, PTX may counteract EMT in cervical cancer cells by decreasing the NF-κB and SERPINE1.
The Role of SOCS3 in Regulating Meat Quality in Jinhua Pigs
Authors: Wu Fen , Chen Zitao , Zhang Zhenyang , Wang Zhen , Zhang Zhe , Wang Qishan , Pan Yuchun
Published: June 2023

Meat quality is an important economic trait that influences the development of the pig industry. Skeletal muscle development and glycolytic potential (GP) are two crucial aspects that significantly impact meat quality. It has been reported that abnormal skeletal muscle development and high glycogen content results in low meat quality. However, the genetic mechanisms underlying these factors are still unclear. Compared with intensive pig breeds, Chinese indigenous pig breeds, such as the Jinhua pig, express superior meat quality characteristics. The differences in the meat quality traits between Jinhua and intensive pig breeds make them suitable for uncovering the genetic mechanisms that regulate meat quality traits. In this study, the Jinhua pig breed and five intensive pig breeds, including Duroc, Landrace, Yorkshire, Berkshire, and Pietrain pig breeds, were selected as experimental materials. First, the FST and XP-EHH methods were used to screen the selective signatures on the genome in the Jinhua population. Then, combined with RNA-Seq data, the study further confirmed that SOCS3 could be a key candidate gene that influences meat quality by mediating myoblast proliferation and glycometabolism because of the down-regulated expression of SOCS3 in Jinhua pigs compared with Landrace pigs. Finally, through SOCS3 knockout (KO) and overexpression (OE) experiments in mouse C2C12 cells, the results showed that SOCS3 regulated the cell proliferation of myoblasts. Moreover, SOCS3 is involved in regulating glucose uptake by the IRS1/PI3K/AKT signaling pathway. Overall, these findings provide a basis for the genetic improvement of meat quality traits in the pig industry.
A FTIR and DFT Combination Study to Reveal the Mechanism of Eliminating the Azeotropy in Ethyl Propionate–n-Propanol System with Ionic Liquid Entrainer
Authors: Zheng Yan-Zhen , Zhao Rui , Zhang Yu-Cang , Zhou Yu
Published: June 2023

Ionic liquids (ILs) have presented excellent behaviors in the separation of azeotropes in extractive distillation. However, the intrinsic molecular nature of ILs in the separation of azeotropic systems is not clear. In this paper, Fourier-transform infrared spectroscopy (FTIR) and theoretical calculations were applied to screen the microstructures of ethyl propionate–n-propanol–1-ethyl-3-methylimidzolium acetate ([EMIM][OAC]) systems before and after azeotropy breaking. A detailed vibrational analysis was carried out on the v(C=O) region of ethyl propionate and v(O–D) region of n-propanol-d1. Different species, including multiple sizes of propanol and ethyl propionate self-aggregators, ethyl propionate–n-propanol interaction complexes, and different IL–n-propanol interaction complexes, were identified using excess spectroscopy and confirmed with theoretical calculations. Their changes in relative amounts were also observed. The hydrogen bond between n-propanol and ethyl propionate/[EMIM][OAC] was detected, and the interaction properties were also revealed. Overall, the intrinsic molecular nature of the azeotropy breaking was clear. First, the interactions between [EMIM][OAC] and n-propanol were stronger than those between [EMIM][OAC] and ethyl propionate, which influenced the relative volatilities of the two components in the system. Second, the interactions between n-propanol and [EMIM][OAC] were stronger than those between n-propanol and ethyl propionate. Hence, adding [EMIM][OAC] could break apart the ethyl propionate–n-propanol complex (causing the azeotropy in the studied system). When x([EMIM][OAC]) was lower than 0.04, the azeotropy still existed mainly because the low IL could not destroy the whole ethyl propionate–n-propanol interaction complex. At x(IL) > 0.04, the whole ethyl propionate–n-propanol complex was destroyed, and the azeotropy disappeared.
Isolation and Optimization of a Broad-Spectrum Synthetic Antimicrobial Peptide, Ap920-WI, from Arthrobacter sp. H5 for the Biological Control of Plant Diseases
Authors: Zhao Li , Islam Md. Samiul , Song Pei , Zhu Li , Dong Wubei
Published: June 2023

Antimicrobial peptides (AMPs) are naturally occurring molecules found in various organisms that can help to defend against invading microorganisms and reduce the likelihood of drug resistance development. This study focused on the isolation of new AMPs from the genome library of a Gram-positive bacterium called Arthrobacter sp. H5. To achieve this, we used the Bacillus subtilis expression system and employed bioinformatics techniques to optimize and modify the peptides, resulting in the development of a new synthetic antimicrobial peptide (SAMP). Ap920 is expected to be a new antimicrobial peptide with a high positive charge (+12.5). Through optimization, a new synthetic antimicrobial peptide, Ap920-WI, containing only 15 amino acids, was created. Thereafter, the antimicrobial and antifungal activities of Ap920-WI were determined using minimum inhibitory concentration (MIC) and the concentration for 50% of maximal effect (EC50). The Ap920-WI peptide was observed to target the outer membrane of fungal hyphae, leading to inhibition of growth in Rhizoctonia Solani, Sclerotinia sclerotiorum, and Botrytis cinerea. In plants, Ap920-WI showed significant antifungal activity and inhibited the infestation of S. sclerotiorum on rape leaves. Importantly, Ap920-WI was found to be safe for mammalian cells since it did not show any hemolytic activity against sheep red blood cells. Overall, the study found that the new synthetic antimicrobial peptide Ap920-WI exhibits broad-spectrum activity against microorganisms and may offer a new solution for controlling plant diseases, as well as hold potential for drug development.