bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortar Characterization of Historical Masonry Damaged by Riverbank Failure: The Case of Lungarno Torrigiani (Florence)
Authors: Calandra Sara , Salvatici Teresa , Pecchioni Elena , Centauro Irene , Garzonio Carlo Alberto
Published: April 2023

The research of structural masonry associated with geo-hydrological hazards in Cultural Heritage is a multidisciplinary issue, requiring consideration of several aspects including the characterization of used materials. On 25 May 2016, loss of water from the subterranean pipes and of the aqueduct caused an Arno riverbank failure damaging a 100 m long portion of the historical embankment wall of Lungarno Torrigiani in Florence. The historical masonry was built from 1854–1855 by Giuseppe Poggi and represents a historical example of an engineering approach to riverbank construction, composed of a scarp massive wall on foundation piles, with a rubble masonry internal core. The failure event caused only a cusp-shaped deformation to the wall without any shattering or toppling. A complete characterization of the mortars was performed to identify the technologies, raw materials and state of conservation in order to understand why the wall has not collapsed. Indeed, the mortars utilized influenced the structural behavior of masonry, and their characterization was fundamental to improve the knowledge of mechanical properties of civil architectural heritage walls. Therefore, the aim of this research was to analyze the mortars from mineralogical–petrographic, physical and mechanical points of view, to evaluate the contribution of the materials to damage events. Moreover, the results of this study helped to identify compatible project solutions for the installation of hydraulically and statically functional structures to contain the riverbank.
Nano-Biochar Suspension Mediated Alterations in Yield and Juice Quality of Kinnow (Citrus reticulata L.)
Authors: Shani Muhammad Yousaf , Ahmed Syed Riaz , Ashraf Muhammad Yasin , Khan Zafran , Cocozza Claudio , De Mastro Francesco , Gul Nimra , Pervaiz Soha , Abbas Shahid , Nawaz Hummera , Brunetti Gennaro
Published: April 2023

Nutrient deficiency negatively affects the yield and quality of citrus fruit. The present experiment was carried out to investigate the improvement in fruit yield and juice quality of Kinnow (Citrus reticulata L.) by foliar application of nano-biochar suspension (NBS). The experiment was carried out in a citrus farmer’s orchard with a history of low fruit yield, using a randomized complete block design. Four NBS treatments, i.e., 0% (control), 1, 3, and 5%, were applied through foliar application at the flowering stage. Foliar application of NBS at 5% and 3% significantly (p < 0.05) improved flowering, fruit retention, fruit set, fruit size, length, weight, diameter, juice volume levels, and minimized fruit dropping. The electrical conductivity of the juice was significantly decreased by increases in NBS concentration. Total dissolved solids increased slightly with treatments as compared to control. However, NBS foliar application did not show significant effects on nitrogen (N), potassium (K), and sodium (Na) leaf contents, but had some effect on phosphorus (P) content. Principal component analysis and a correlation matrix revealed significant (p < 0.05) positive and negative associations among the studied traits. The results of the current experiment showed that all parameters were significantly improved with the application of NBS at 3 and 5%, except that N, K, and Na levels were unaffected. The most encouraging results were achieved at a concentration of 5% NBS. In conclusions, the foliar application of NBS had a significant positive impact on fruit yield and juice quality.
Free Volatile Compounds as Chemophenetic Markers—Comparison with ITS2 and ITS1-5.8S-ITS2 Sequence Data for 18 Species of the Genus Veronica
Authors: Nazlić Marija , Kremer Dario , Fredotović Željana , Trumbić Željka , Dunkić Valerija , Puizina Jasna
Published: April 2023

(1) Background: The purpose of this study was to compare the free volatile compounds of 18 Veronica species (Plantaginaceae), as previously analyzed by gas chromatography coupled with mass spectrometry, with their DNA sequences for internal transcribed spacers ITS2 and ITS1-5.8S-ITS2 of the nuclear ribosomal DNA. (2) Methods: Two sets of DNA sequence data were generated and used for phylogenetic analysis: ITS2 sequences (~360 bp) obtained by next-generation sequencing and ITS1-5.8S-ITS2 sequences (~580 bp) sequenced by the Sanger sequencing method. Clustering from previously analyzed free volatile compounds was performed by Ward’s method. (3) Results: Both sets of DNA sequence data showed that the 18 analyzed Veronica species were grouped into eight main groups corresponding to the following subgenera: Pentasepalae, Pocilla, Chamaedrys, Veronica, Beccabunga, Cochlidiosperma, Stenocarpon and Pseudolysimachium. Results of the clustering analysis of free volatile compounds showed better clustering when using microwave-extracted volatiles. Three clusters were detected with the following main compounds: hexahydrofarnesyl acetone, hexadecanoic acid, phytol, caryophyllene oxide and (E)-caryophyllene. (4) Conclusion: The phylogenetic analysis of ITS2 data obtained by NGS technology and ITS1-5.8S-ITS2 data obtained by Sanger sequencing resulted in the grouping of 18 Veronica species into eight subgenera, which is in accordance with the existing classification. Statistical testing showed that there was no correlation between such clustering of Veronica species and clustering that was based on free volatile compounds. The achieved results can be viewed in the light of parallel evolution among some of the species of the Veronica genus as well as the fact that volatile compound composition can be influenced by environmental factors or epigenetic modifications.
Flowering Response of Cannabis sativa L. ‘Suver Haze’ under Varying Daylength-Extension Light Intensities and Durations
Authors: Park Jongseok , Collado Cristian E. , Lam Vu Phong , Hernández Ricardo
Published: April 2023

Daylength-extension lighting (DE) is used in the cannabis industry to increase plant size and produce cuttings by regulating flowering and extending the vegetative stage. Growers have reported incomplete or transitional inflorescences in several Cannabis cultivars even when exposed to long photoperiods. Cannabis sativa L. ‘Suver Haze’ has been reported to develop incomplete inflorescences in North Carolina nurseries using photoperiods of 15 h. The objectives of this study were to investigate the required light intensity and photoperiod to inhibit the flowering of ‘Suver Haze’. In Experiment 1, DE of 1.0, 2.5, 5.8, and 10.3 µmol·m−2·s−1 of photosynthetic photon flux density from incandescent lamps were used to extend the photoperiod of ‘Suver Haze’ from 9 to 15 h. A 9 h photoperiod control was included. The results showed that all DE treatments stopped the full transition to flowering compared to the control; however, all DE-treated plants showed the presence of incomplete inflorescences. In Experiment 2, three photoperiod treatments of 15 h, 18 h, and 21 h were tested. ‘Suver Haze’ under 18 h and 21 h photoperiods did not develop incomplete inflorescences in contrast to plants in 15 h photoperiod. Therefore, a light intensity of at least 1.0 µmol·m−2·s−1 PPFD and an 18 h photoperiod are required to prevent incomplete inflorescences and flowering of ‘Suver Haze’.
Effect of Nisin on the Quality and Antioxidant Activity of Fresh-Cut Pumpkins (Cucurbita moschata Duch.)
Authors: Yuan Ning , Wang Yi , Guan Yuge , Chen Chen , Hu Wenzhong
Published: April 2023

Fresh-cut pumpkins refer to fresh pumpkin that has been graded, cleaned, peeled, sliced, preserved, and packaged. It has the qualities of freshness, nutrition, convenience, and being 100% edible. However, mechanical damages during the cutting processing can accelerate the quality deterioration, aging, and loss of nutritional values of fresh-cut pumpkins. Nisin, a natural preservative, has been widely used in fruits and vegetables with good preservation effects. To investigate the effect of different concentrations (0, 0.2, 0.4, and 0.6 g/L) of nisin on the quality of fresh-cut pumpkins, the critical indexes involved in weight loss, firmness, color, respiration intensity, reactive oxygen species (ROS) metabolism, ascorbate (AsA)—glutathione (GSH) cycle, and antioxidant capacity were monitored for fresh-cut pumpkins during storage at 4 °C for 10 days. The results showed that 0.4 g/L nisin was the best preservation concentration. Compared with 0 g/L nisin, 0.4 g/L nisin reduced the weight loss rate and whitening rate of fresh-cut pumpkins by 13.53% and 13.61%, inhibited respiration rate by 45.83%, and maintained hardness by 1.18 times. Meanwhile, 0.4 g/L nisin increased the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) and maintained higher contents of GSH and AsA. It prevented the rapid increase in ROS levels by improving antioxidant capacity, including DPPH, ABTS free radical scavenging rate, and T-AOC (total antioxidant capacity). The collected results showed that nisin has an obvious influence on the quality by regulating physiological and antioxidant activity metabolism. It is envisaged that the combination of nisin and physical and chemical preservation technology will further enhance the quality of fresh-cut pumpkins during storage in the future.
Driving Behaviour in Depression Based on Subjective Evaluation and Data from a Driving Simulator
Authors: Tsoutsi Vagioula , Papadakaki Maria , Yannis George , Pavlou Dimosthenis , Basta Maria , Chliaoutakis Joannes , Dikeos Dimitris
Published: April 2023

Road traffic collisions are a major issue for public health. Depression is characterized by mental, emotional and executive dysfunction, which may have an impact on driving behaviour. Patients with depression (N = 39) and healthy controls (N = 30) were asked to complete questionnaires and to drive on a driving simulator in different scenarios. Driving simulator data included speed, safety distance from the preceding vehicle and lateral position. Demographic and medical information, insomnia (Athens Insomnia Scale, AIS), sleepiness (Epworth Sleepiness Scale, ESS), fatigue (Fatigue Severity Scale, FSS), symptoms of sleep apnoea (StopBang Questionnaire) and driving (Driver Stress Inventory, DSI and Driver Behaviour Questionnaire, DBQ) were assessed. Gender and age influenced almost all variables. The group of patients with depression did not differ from controls regarding driving behaviour as assessed through questionnaires; on the driving simulator, patients kept a longer safety distance. Subjective fatigue was positively associated with aggression, dislike of driving, hazard monitoring and violations as assessed by questionnaires. ESS and AIS scores were positively associated with keeping a longer safety distance and with Lateral Position Standard Deviation (LPSD), denoting lower ability to keep a stable position. It seems that, although certain symptoms of depression (insomnia, fatigue and somnolence) may affect driving performance, patients drive more carefully eliminating, thus, their impact.
“Our Mothers Have Handed That to Us. Her Mother Has Handed That to Her”: Urban Aboriginal and Torres Strait Islander Yarning about Community Wellbeing, Healthy Pregnancies, and the Prevention of Fetal Alcohol Spectrum Disorder
Authors: Lyall Vivian , Egert Sonya , Reid Natasha , Moritz Karen , Askew Deborah
Published: April 2023

In Australia, fetal alcohol spectrum disorder (FASD) is a largely hidden disability that is currently under-recognized, under-resourced, and under- or misdiagnosed. Unsurprisingly, efforts to prevent FASD in urban Aboriginal and Torres Strait Islander communities are lacking. Further, mainstream approaches are not compatible with diverse and distinct Aboriginal and Torres Strait Islander ways of approaching family, pregnancy, and parenting life. To support the creation of culturally appropriate urban Aboriginal and Torres Strait Islander FASD prevention strategies, we sought to understand local perspectives, experiences, and priorities for supporting healthy and alcohol-free pregnancies. Using a narrative methodology, we undertook research yarns with eight female and two male community participants. Data were analyzed using a narrative, thematic analysis and guided by an Indigenist research practice of reflexive listening. Participant yarns provided important insights into local urban Aboriginal and Torres Strait Islander cultural, social, and structural determinants that support family and child health, alcohol-free pregnancies, and the prevention of FASD. The results provide critical guidance for Indigenizing and decolonizing FASD prevention strategies to support culturally safe, relevant, and strengths-based services. This approach has critical implications for all health and social professionals and can contribute to Aboriginal and Torres Strait Islander peoples’ justice, recovery, and healing from colonization.
The Twelve Ds: An Update to Edwards and Benson’s Reasons for Non-Parental Caregiving
Authors: Lopez Acacia R. , Nadorff Danielle K. , Peters Delaney
Published: April 2023

This qualitative study examined the prevalence of the “Nine Ds,” a framework developed by Edwards and Benson for understanding the heterogeneity of reasons for which grandparents assume care of grandchildren (i.e., death, disease, detention, divorce, departure, drugs, desertion, delivery, deployment) in a contemporary sample. Using a nationwide sample of custodial grandparents (N = 322) and foster parents (N = 105), caregivers were asked their reason for assuming care of the grandchild or foster child within their care. The results of the study suggest that the Nine Ds are a useful framework, but accounted for only 21.74% of responses, indicating the Nine Ds fail to capture many of the reasons for assuming care. Three new themes—dollars, duty, and daily grind—were identified using semantic thematic analysis and are applicable to both grandfamilies and foster families. These themes represent different motivations for assuming care and provide insight into the social structures that may act as barriers to family formation. This study provides a foundation for future research examining the impact of assumed care by non-parental attachment figures on the health and well-being of both grandchildren and foster children.
Virtual Reality for Addressing Depression and Anxiety: A Bibliometric Analysis
Authors: Jingili Nuru , Oyelere Solomon Sunday , Ojwang Frank , Agbo Friday Joseph , Nyström Markus B. T.
Published: April 2023

Virtual reality is an emerging field in mental health and has gained widespread acceptance due to its potential to treat various disorders, such as anxiety and depression. This paper presents a bibliometric analysis of virtual reality (VR) use in addressing depression and anxiety from 1995 to 2022. The study analysed 1872 documents using the Scopus database, identifying the field’s most relevant journals and authors. The results indicate that using VR for addressing anxiety and depression is a multidisciplinary field with a wide variety of research topics, leading to significant collaborative research in this area. The Annual Review of Cybertherapy and Telemedicine was identified as the most relevant journal, while Behavior Research and Therapy was found to be the most cited journal. The analysis of keywords suggests that there is more research on using VR for anxiety and related disorders than for depression. Riva G. was identified as the top author in producing research outputs on VR-AD, and the University of Washington emerged as the leading institution in scientific outputs on VR-AD. Thematic and intellectual analyses helped identify the main themes within the research domain, providing valuable insight into the current and future directions of the field.
Ferroptosis in Haematological Malignancies and Associated Therapeutic Nanotechnologies
Authors: Mynott Rachel L. , Habib Ali , Best Oliver G. , Wallington-Gates Craig T.
Published: April 2023

Haematological malignancies are heterogeneous groups of cancers of the bone marrow, blood or lymph nodes, and while therapeutic advances have greatly improved the lifespan and quality of life of those afflicted, many of these cancers remain incurable. The iron-dependent, lipid oxidation-mediated form of cell death, ferroptosis, has emerged as a promising pathway to induce cancer cell death, particularly in those malignancies that are resistant to traditional apoptosis-inducing therapies. Although promising findings have been published in several solid and haematological malignancies, the major drawbacks of ferroptosis-inducing therapies are efficient drug delivery and toxicities to healthy tissue. The development of tumour-targeting and precision medicines, particularly when combined with nanotechnologies, holds potential as a way in which to overcome these obstacles and progress ferroptosis-inducing therapies into the clinic. Here, we review the current state-of-play of ferroptosis in haematological malignancies as well as encouraging discoveries in the field of ferroptosis nanotechnologies. While the research into ferroptosis nanotechnologies in haematological malignancies is limited, its pre-clinical success in solid tumours suggests this is a very feasible therapeutic approach to treat blood cancers such as multiple myeloma, lymphoma and leukaemia.
The ACE rs1799752 Variant Is Associated with COVID-19 Severity but Is Independent of Serum ACE Activity in Hospitalized and Recovered Patients
Authors: Fricke-Galindo Ingrid , Buendia-Roldan Ivette , Ponce-Aguilar Daniel I. , Pérez-Rubio Gloria , Chavez-Galan Leslie , Alanis-Ponce Jesús , Pérez-Torres Karina , Valencia-Pérez Rea Daniela , Téllez-Quijada Fernanda , Nava-Quiroz Karol J. , Hernández-Zenteno Rafael de Jesús , Gutiérrez-Nava Angélica , Falfán-Valencia Ramcés
Published: April 2023

This paper assesses the association of the insertion/deletion ACE (angiotensin-converting enzyme) variant (rs1799752 I/D) and the serum ACE activity with the severity of COVID-19 as well as its impact on post-COVID-19, and we compare these associations with those for patients with non-COVID-19 respiratory disorders. We studied 1252 patients with COVID-19, 104 subjects recovered from COVID-19, and 74 patients hospitalized with a respiratory disease different from COVID-19. The rs1799752 ACE variant was assessed using TaqMan® Assays. The serum ACE activity was determined using a colorimetric assay. The DD genotype was related to risk for invasive mechanical ventilation (IMV) requirement as an indicator of COVID-19 severity when compared to the frequencies of II + ID genotypes (p = 0.025, OR = 1.428, 95% CI = 1.046–1.949). In addition, this genotype was significantly higher in COVID-19 and post-COVID-19 groups than in the non-COVID-19 subjects. The serum ACE activity levels were lower in the COVID-19 group (22.30 U/L (13.84–32.23 U/L)), which was followed by the non-COVID-19 (27.94 U/L (20.32–53.36 U/L)) and post-COVID-19 subjects (50.00 U/L (42.16–62.25 U/L)). The DD genotype of the rs1799752 ACE variant was associated with the IMV requirement in patients with COVID-19, and low serum ACE activity levels could be related to patients with severe disease.
The Pathophysiological Role of Thymosin β4 in the Kidney Glomerulus
Authors: Mason William J. , Vasilopoulou Elisavet
Published: April 2023

Diseases affecting the glomerulus, the filtration unit of the kidney, are a major cause of chronic kidney disease. Glomerular disease is characterised by injury of glomerular cells and is often accompanied by an inflammatory response that drives disease progression. New strategies are needed to slow the progression to end-stage kidney disease, which requires dialysis or transplantation. Thymosin β4 (Tβ4), an endogenous peptide that sequesters G-actin, has shown potent anti-inflammatory function in experimental models of heart, kidney, liver, lung, and eye injury. In this review, we discuss the role of endogenous and exogenous Tβ4 in glomerular disease progression and the current understanding of the underlying mechanisms.
Structural Characterization of Several Cement-Based Materials Containing Chemical Additives with Potential Application in Additive Manufacturing
Authors: Simedru Alexandru Florin , Becze Anca , Cadar Oana , Scurtu Daniela Alexandra , Simedru Dorina , Ardelean Ioan
Published: April 2023

The rapid increase in additive manufacturing applications in all industries has highlighted the lack of innovative technologies and processes in the construction industry. Several European and international policies are in place to guide the development of the technological processes involved in the construction industry toward a sustainable future. Considering the global concerns regarding this industry, the purpose of this study was to develop new cement-based materials that are capable of accelerated hydration and early strength development for use in additive manufacturing. Ca(NO3)2·4H2O, Al2(SO4)3·18H2O and Na2S2O3·5H2O were used to obtain the accelerating effect in the hydration of Portland cement. Based on results obtained from X-ray diffraction (XRD), scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM/EDX) techniques, as well as low-field nuclear magnetic resonance relaxometry (LF-NMR) techniques, it was demonstrated that all accelerators used have a quickening effect on cement hydration. The addition of Na2S2O3·5H2O or combined Na2S2O3·5H2O and Ca(NO3)2·4H2O led to obtaining new cement-based materials with early strength development and fast hydration of microorganized internal structures, critical characteristics for 3D printing.
DUSP6 Deficiency Attenuates Neurodegeneration after Global Cerebral Ischemia
Authors: Weng Yi-Chinn , Huang Yu-Ting , Chiang I-Chen , Chuang Huai-Chia , Lee Tsong-Hai , Tan Tse-Hua , Chou Wen-Hai
Published: April 2023

Transient global cerebral ischemia (tGCI) resulting from cardiac arrest causes selective neurodegeneration in hippocampal CA1 neurons. Although the effect is clear, the underlying mechanisms directing this process remain unclear. Previous studies have shown that phosphorylation of Erk1/2 promotes cell survival in response to tGCI. DUSP6 (also named MKP3) serves as a cytosolic phosphatase that dephosphorylates Erk1/2, but the role of DUSP6 in tGCI has not been characterized. We found that DUSP6 was specifically induced in the cytoplasm of hippocampal CA1 neurons 4 to 24 h after tGCI. DUSP6-deficient mice showed normal spatial memory acquisition and retention in the Barnes maze. Impairment of spatial memory acquisition and retention after tGCI was attenuated in DUSP6-deficient mice. Neurodegeneration after tGCI, revealed by Fluoro-Jade C and H&E staining, was reduced in the hippocampus of DUSP6-deficient mice and DUSP6 deficiency enhanced the phosphorylation and nuclear translocation of Erk1/2 in the hippocampal CA1 region. These data support the role of DUSP6 as a negative regulator of Erk1/2 signaling and indicate the potential of DUSP6 inhibition as a novel therapeutic strategy to treat neurodegeneration after tGCI.
Study on the Flower Induction Mechanism of Hydrangea macrophylla
Authors: Liu Yun , Lyu Tong , Lyu Yingmin
Published: April 2023

The flower induction of Hydrangea macrophylla “Endless Summer” is regulated by a complex gene network that involves multiple signaling pathways to ensure continuous flowering throughout the growing season, but the molecular determinants of flower induction are not yet clear. In this study, genes potentially involved in signaling pathway mediating the regulatory mechanism of flower induction were identified through the transcriptomic profiles, and a hypothetical model for this regulatory mechanism was obtained by an analysis of the available transcriptomic data, suggesting that sugar-, hormone-, and flowering-related genes participated in the flower induction process of H. macrophylla “Endless Summer”. The expression profiles of the genes involved in the biosynthesis and metabolism of sugar showed that the beta-amylase gene BAM1 displayed a high expression level at the BS2 stage and implied the hydrolysis of starch. It may be a signaling molecule that promotes the transition from vegetative growth to reproductive growth in H. macrophylla “Endless Summer”. Complex hormone regulatory networks involved in abscisic acid (ABA), auxin (IAA), zeatin nucleoside (ZR), and gibberellin (GA) also induced flower formation in H. macrophylla. ABA participated in flower induction by regulating flowering genes. The high content of IAA and the high expression level of the auxin influx carrier gene LAX5 at the BS2 stage suggested that the flow of auxin between sources and sinks in H. macrophylla is involved in the regulation of floral induction as a signal. In addition, flowering-related genes were mainly involved in the photoperiodic pathway, the aging pathway, and the gibberellin pathway. As a result, multiple pathways, including the photoperiodic pathway, the aging pathway, and the gibberellin pathway, which were mainly mediated by crosstalk between sugar and hormone signals, regulated the molecular network involved in flower induction in H. macrophylla “Endless Summer”.
Sustainable Valorization of Bioplastic Waste: A Review on Effective Recycling Routes for the Most Widely Used Biopolymers
Authors: Bartolucci Lorenzo , Cordiner Stefano , De Maina Emanuele , Kumar Gopalakrishnan , Mele Pietro , Mulone Vincenzo , Igliński Bartłomiej , Piechota Grzegorz
Published: April 2023

Plastics-based materials have a high carbon footprint, and their disposal is a considerable problem for the environment. Biodegradable bioplastics represent an alternative on which most countries have focused their attention to replace of conventional plastics in various sectors, among which food packaging is the most significant one. The evaluation of the optimal end-of-life process for bioplastic waste is of great importance for their sustainable use. In this review, the advantages and limits of different waste management routes—biodegradation, mechanical recycling and thermal degradation processes—are presented for the most common categories of biopolymers on the market, including starch-based bioplastics, PLA and PBAT. The analysis outlines that starch-based bioplastics, unless blended with other biopolymers, exhibit good biodegradation rates and are suitable for disposal by composting, while PLA and PBAT are incompatible with this process and require alternative strategies. The thermal degradation process is very promising for chemical recycling, enabling building blocks and the recovery of valuable chemicals from bioplastic waste, according to the principles of a sustainable and circular economy. Nevertheless, only a few articles have focused on this recycling process, highlighting the need for research to fully exploit the potentiality of this waste management route.
The RING-Finger Protein NbRFP1 Contributes to Regulating the Host Hypersensitive Response Induced by Oat Dwarf Virus RepA
Authors: Liang Yanqing , Wang Zhanqi , Wang Qian , Zhou Xueping , Qian Yajuan
Published: April 2023

Our previous study identified that the RepA protein encoded by the oat dwarf virus (ODV) was responsible for inducing a strong hypersensitive response (HR) during the virus infection in non-host tobacco plants. However, little was known about the molecular mechanism of the RepA-elicited HR. Here, a RING-finger protein, which is described as NbRFP1 and is mainly located in the cytoplasm and nucleus in Nicotiana benthamiana cells, was confirmed to interact with RepA. In addition, the accumulation level of NbRFP1 in N. benthamiana leaves was enhanced by either ODV infection or by only RepA expression. The knockdown of NbRFP1 by a TRV-mediated virus-induced gene silencing markedly delayed the ODV or RepA-elicited HR. By contrast, the overexpression of NbRFP1 in N. benthamiana conferred enhanced resistance to ODV infection and promoted RepA-induced HR. Further mutation analysis showed that a RING-finger domain located in NbRFP1 plays important roles in modulating RepA-induced HR, as well as in mediating the interaction between NbRFP1 and RepA.
ADAM17 Confers Temozolomide Resistance in Human Glioblastoma Cells and miR-145 Regulates Its Expression
Authors: Yang Jen-Tsung , Lee I-Neng , Huang Cheng , Huang Hsiu-Chen , Wu Yu-Ping , Chong Zhi-Yong , Chen Jui-Chieh
Published: April 2023

Glioblastoma (GBM) is a malignant brain tumor, commonly treated with temozolomide (TMZ). Upregulation of A disintegrin and metalloproteinases (ADAMs) is correlated to malignancy; however, whether ADAMs modulate TMZ sensitivity in GBM cells remains unclear. To explore the role of ADAMs in TMZ resistance, we analyzed changes in ADAM expression following TMZ treatment using RNA sequencing and noted that ADAM17 was markedly upregulated. Hence, we established TMZ-resistant cell lines to elucidate the role of ADAM17. Furthermore, we evaluated the impact of ADAM17 knockdown on TMZ sensitivity in vitro and in vivo. Moreover, we predicted microRNAs upstream of ADAM17 and transfected miRNA mimics into cells to verify their effects on TMZ sensitivity. Additionally, the clinical significance of ADAM17 and miRNAs in GBM was analyzed. ADAM17 was upregulated in GBM cells under serum starvation and TMZ treatment and was overexpressed in TMZ-resistant cells. In in vitro and in vivo models, ADAM17 knockdown conferred greater TMZ sensitivity. miR-145 overexpression suppressed ADAM17 and sensitized cells to TMZ. ADAM17 upregulation and miR-145 downregulation in clinical specimens are associated with disease progression and poor prognosis. Thus, miR-145 enhances TMZ sensitivity by inhibiting ADAM17. These findings offer insights into the development of therapeutic approaches to overcome TMZ resistance.
NADPH Oxidase Subunit CYBB Confers Chemotherapy and Ferroptosis Resistance in Mesenchymal Glioblastoma via Nrf2/SOD2 Modulation
Authors: Su I-Chang , Su Yu-Kai , Setiawan Syahru Agung , Yadav Vijesh Kumar , Fong Iat-Hang , Yeh Chi-Tai , Lin Chien-Min , Liu Heng-Wei
Published: April 2023

Glioblastoma multiforme (GBM) is a highly heterogeneous disease with a mesenchymal subtype tending to exhibit more aggressive and multitherapy-resistant features. Glioblastoma stem-cells derived from mesenchymal cells are reliant on iron supply, accumulated with high reactive oxygen species (ROS), and susceptible to ferroptosis. Temozolomide (TMZ) treatment is the mainstay drug for GBM despite the rapid development of resistance in mesenchymal GBM. The main interconnection between mesenchymal features, TMZ resistance, and ferroptosis are poorly understood. Herein, we demonstrated that a subunit of NADPH oxidase, CYBB, orchestrated mesenchymal shift and promoted TMZ resistance by modulating the anti-ferroptosis circuitry Nrf2/SOD2 axis. Public transcriptomic data re-analysis found that CYBB and SOD2 were highly upregulated in the mesenchymal subtype of GBM. Accordingly, our GBM cohort confirmed a high expression of CYBB in the GBM tumor and was associated with mesenchymal features and poor clinical outcome. An in vitro study demonstrated that TMZ-resistant GBM cells displayed mesenchymal and stemness features while remaining resilient to erastin-mediated ferroptosis by activating the CYBB/Nrf2/SOD2 axis. The CYBB maintained a high ROS state to sustain the mesenchymal phenotype, TMZ resistance, and reduced erastin sensitivity. Mechanistically, CYBB interacted with Nrf2 and consequently regulated SOD2 transcription. Compensatory antioxidant SOD2 essentially protected against the deleterious effect of high ROS while attenuating ferroptosis in TMZ-resistant cells. An animal study highlighted the protective role of SOD2 to mitigate erastin-triggered ferroptosis and tolerate oxidative stress burden in mice harboring TMZ-resistant GBM cell xenografts. Therefore, CYBB captured ferroptosis resilience in mesenchymal GBM. The downstream compensatory activity of CYBB via the Nrf2/SOD2 axis is exploitable through erastin-induced ferroptosis to overcome TMZ resistance.
Promotive Effect of FBXO32 on the Odontoblastic Differentiation of Human Dental Pulp Stem Cells
Authors: Xu Ke , Liu Qin , Huang Wushuang , Chu Yanhao , Fan Wenguo , Liu Jiawei , He Yifan , Huang Fang
Published: April 2023

Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) is crucial for the intricate formation and repair processes in dental pulp. Until now, the literature is not able to demonstrate the role of ubiquitination in the odontoblastic differentiation of hDPSCs. This study investigated the role of F-box-only protein 32 (FBXO32), an E3 ligase, in the odontoblastic differentiation of hDPSCs. The mRNA expression profile was obtained from ribonucleic acid sequencing (RNA-Seq) data and analyzed. Immunofluorescence and immunohistochemical staining identify the FBXO32 expression in human dental pulp and hDPSCs. Small-hairpin RNA lentivirus was used for FBXO32 knockdown and overexpression. Odontoblastic differentiation of hDPSCs was determined via alkaline phosphatase activity, Alizarin Red S staining, and mRNA and protein expression levels were detected using real-time quantitative polymerase chain reaction and Western blotting. Furthermore, subcutaneous transplantation in nude mice was performed to evaluate the role of FBXO32 in mineralization in vivo using histological analysis. FBXO32 expression was upregulated in the odontoblast differentiated hDPSCs as evidenced by RNA-Seq data analysis. FBXO32 was detected in hDPSCs and the odontoblast layer of the dental pulp. Increased FBXO32 expression in hDPSCs during odontoblastic differentiation was confirmed. Through lentivirus infection method, FBXO32 downregulation in hDPSCs attenuated odontoblastic differentiation in vitro and in vivo, whereas FBXO32 upregulation promoted the hDPSCs odontoblastic differentiation, without affecting proliferation and migration. This study demonstrated, for the first time, the promotive role of FBXO32 in regulating the odontoblastic differentiation of hDPSCs, thereby providing novel insights into the regulatory mechanisms during odontoblastic differentiation in hDPSCs.
3D Visualization, Skeletonization and Branching Analysis of Blood Vessels in Angiogenesis
Authors: Ramakrishnan Vignesh , Schönmehl Rebecca , Artinger Annalena , Winter Lina , Böck Hendrik , Schreml Stephan , Gürtler Florian , Daza Jimmy , Schmitt Volker H. , Mamilos Andreas , Arbelaez Pablo , Teufel Andreas , Niedermair Tanja , Topolcan Ondrej , Karlíková Marie , Sossalla Samuel , Wiedenroth Christoph B. , Rupp Markus , Brochhausen Christoph
Published: April 2023

Angiogenesis is the process of new blood vessels growing from existing vasculature. Visualizing them as a three-dimensional (3D) model is a challenging, yet relevant, task as it would be of great help to researchers, pathologists, and medical doctors. A branching analysis on the 3D model would further facilitate research and diagnostic purposes. In this paper, a pipeline of vision algorithms is elaborated to visualize and analyze blood vessels in 3D from formalin-fixed paraffin-embedded (FFPE) granulation tissue sections with two different staining methods. First, a U-net neural network is used to segment blood vessels from the tissues. Second, image registration is used to align the consecutive images. Coarse registration using an image-intensity optimization technique, followed by finetuning using a neural network based on Spatial Transformers, results in an excellent alignment of images. Lastly, the corresponding segmented masks depicting the blood vessels are aligned and interpolated using the results of the image registration, resulting in a visualized 3D model. Additionally, a skeletonization algorithm is used to analyze the branching characteristics of the 3D vascular model. In summary, computer vision and deep learning is used to reconstruct, visualize and analyze a 3D vascular model from a set of parallel tissue samples. Our technique opens innovative perspectives in the pathophysiological understanding of vascular morphogenesis under different pathophysiological conditions and its potential diagnostic role.
Myeloperoxidase in Health and Disease
Authors: Ortiz-Cerda Tamara , Xie Kangzhe , Mojadadi Albaraa , Witting Paul K.
Published: April 2023

Innate and adaptive immune responses comprise a complex network of protein–protein and protein–cell interactions that regulates commensal flora and protects organisms from foreign pathogens and transformed (proliferating) host cells under physiological conditions such as pregnancy, growth and development as well as formulating a response pathological challenge [...]
FDA-Approved Fluorinated Heterocyclic Drugs from 2016 to 2022
Authors: Rizzo Carla , Amata Sara , Pibiri Ivana , Pace Andrea , Buscemi Silvestre , Palumbo Piccionello Antonio
Published: April 2023

The inclusion of fluorine atoms or heterocyclic moiety into drug structures represents a recurrent motif in medicinal chemistry. The combination of these two features is constantly appearing in new molecular entities with various biological activities. This is demonstrated by the increasing number of newly synthesized fluorinated heterocyclic compounds among the Food and Drug Administration FDA-approved drugs. In this review, the biological activity, as well as the synthetic aspects, of 33 recently FDA-approved fluorinated heterocyclic drugs from 2016 to 2022 are highlighted.
Saline-Alkali Soil Property Improved by the Synergistic Effects of Priestia aryabhattai JL-5, Staphylococcus pseudoxylosus XW-4, Leymus chinensis and Soil Microbiota
Authors: Wang Yujue , Wang Yan , Zhang Qian , Fan Hangzhe , Wang Xinyu , Wang Jianan , Zhou Ying , Chen Zhanyu , Sun Fengjie , Cui Xiyan
Published: April 2023

Two saline-alkali-tolerant bacterial strains, Priestia aryabhattai JL-5 and Staphylococcus pseudoxylosus XW-4, were isolated, with high capabilities of hydrolyzing phosphate and producing cellulase, respectively. The molecular mechanisms regulating the saline-alkali tolerance in the strain JL-5 were further investigated using transcriptome analysis. The contents of lactic acid and proline and the enzymatic activity of glutamine synthetase in the strain JL-5 were significantly increased. The properties of saline-alkali soils were significantly improved by the enhanced growth of the indicator plant Leymus chinensis under the combined applications of the strains JL-5 and XW-4 mixed with corn straw. The contents of catalase, peroxidase, superoxide dismutase and proline of L. chinensis were significantly increased, and the content of malondialdehyde was significantly decreased in the combined treatment of both bacterial strains. The contents of available nitrogen, phosphorus and potassium and organic matters in the soil treated with both strains were significantly increased, as well as the diversity and abundance of the soil microbiota. Our study evidently demonstrated the synergistic effects of the strains JL-5 and XW-4, indicator plants and the local microbiota in terms of improving the saline-alkali soil properties, providing strong experimental evidence to support the commercial development of the combined application of both strains to improve the properties of saline-alkali soils.
Natural Killer Cells and Their Implications in Immune Response Diversification in Clinical Pathology and Neoplastic Processes
Authors: Legaz Isabel , Muro Manuel
Published: April 2023

Numerous studies have examined the function of human immune system biomarkers regarding susceptibility, and prognostic, therapeutic, and predictive factors, in various solid and liquid tumors [...]
Advances in Application of Cellulose—MOF Composites in Aquatic Environmental Treatment: Remediation and Regeneration
Authors: Tao Yehan , Du Jian , Cheng Yi , Lu Jie , Min Douyong , Wang Haisong
Published: April 2023

Metal organic frameworks (MOFs) have gained remarkable interest in water treatment due to their fascinating characteristics, such as tunable functionality, large specific surface area, customizable pore size and porosity, and good chemical and thermal stability. However, MOF particles tend to easily agglomerate in nanoscale, thus decreasing their activity and processing convenience. It is necessary to shape MOF nanocrystals into maneuverable structures. The in situ growth or ex situ incorporation of MOFs into inexpensive and abundant cellulose-family materials can be effective strategies for the stabilization of these MOF species, and therefore can make available a range of enhanced properties that expand the industrial application possibilities of cellulose and MOFs. This paper provides a review of studies on recent advances in the application of multi-dimensional MOF–cellulose composites (e.g., aerogels, membranes, and bulk materials) in wastewater remediation (e.g., metals, dyes, drugs, antibiotics, pesticides, and oils) and water regeneration by adsorption, photo- or chemocatalysis, and membrane separation strategies. The advantages brought about by combining MOFs and cellulose are described, and the performance of MOF–cellulose is described and compared to its counterparts. The mechanisms of relative MOF–cellulose materials in processing aquatic pollutants are included. Existing challenges and perspectives for future research are proposed.
From Deep Mutational Mapping of Allosteric Protein Landscapes to Deep Learning of Allostery and Hidden Allosteric Sites: Zooming in on “Allosteric Intersection” of Biochemical and Big Data Approaches
Authors: Verkhivker Gennady , Alshahrani Mohammed , Gupta Grace , Xiao Sian , Tao Peng
Published: April 2023

The recent advances in artificial intelligence (AI) and machine learning have driven the design of new expert systems and automated workflows that are able to model complex chemical and biological phenomena. In recent years, machine learning approaches have been developed and actively deployed to facilitate computational and experimental studies of protein dynamics and allosteric mechanisms. In this review, we discuss in detail new developments along two major directions of allosteric research through the lens of data-intensive biochemical approaches and AI-based computational methods. Despite considerable progress in applications of AI methods for protein structure and dynamics studies, the intersection between allosteric regulation, the emerging structural biology technologies and AI approaches remains largely unexplored, calling for the development of AI-augmented integrative structural biology. In this review, we focus on the latest remarkable progress in deep high-throughput mining and comprehensive mapping of allosteric protein landscapes and allosteric regulatory mechanisms as well as on the new developments in AI methods for prediction and characterization of allosteric binding sites on the proteome level. We also discuss new AI-augmented structural biology approaches that expand our knowledge of the universe of protein dynamics and allostery. We conclude with an outlook and highlight the importance of developing an open science infrastructure for machine learning studies of allosteric regulation and validation of computational approaches using integrative studies of allosteric mechanisms. The development of community-accessible tools that uniquely leverage the existing experimental and simulation knowledgebase to enable interrogation of the allosteric functions can provide a much-needed boost to further innovation and integration of experimental and computational technologies empowered by booming AI field.
A Photoactivated Ru (II) Polypyridine Complex Induced Oncotic Necrosis of A549 Cells by Activating Oxidative Phosphorylation and Inhibiting DNA Synthesis as Revealed by Quantitative Proteomics
Authors: Zhu Li , Liu Hui , Dou Yang , Luo Qun , Gu Liangzhen , Liu Xingkai , Zhou Qianxiong , Han Juanjuan , Wang Fuyi
Published: April 2023

The ruthenium polypyridine complex [Ru(dppa)2(pytp)] (PF6)2 (termed as ZQX-1), where dppa = 4,7-diphenyl-1,10-phenanthroline and pytp = 4′-pyrene-2,2′:6′,2′′-terpyridine, has been shown a high and selective cytotoxicity to hypoxic and cisplatin-resistant cancer cells either under irradiation with blue light or upon two-photon excitation. The IC50 values of ZQX-1 towards A549 cancer cells and HEK293 health cells are 0.16 ± 0.09 µM and >100 µM under irradiation at 420 nm, respectively. However, the mechanism of action of ZQX-1 remains unclear. In this work, using the quantitative proteomics method we identified 84 differentially expressed proteins (DEPs) with |fold-change| ≥ 1.2 in A549 cancer cells exposed to ZQX-1 under irradiation at 420 nm. Bioinformatics analysis of the DEPs revealed that photoactivated ZQX-1 generated reactive oxygen species (ROS) to activate oxidative phosphorylation signaling to overproduce ATP; it also released ROS and pyrene derivative to damage DNA and arrest A549 cells at S-phase, which synergistically led to oncotic necrosis and apoptosis of A549 cells to deplete excess ATP, evidenced by the elevated level of PRAP1 and cleaved capase-3. Moreover, the DNA damage inhibited the expression of DNA repair-related proteins, such as RBX1 and GPS1, enhancing photocytotoxicity of ZQX-1, which was reflected in the inhibition of integrin signaling and disruption of ribosome assembly. Importantly, the photoactivated ZQX-1 was shown to activate hypoxia-inducible factor 1A (HIF1A) survival signaling, implying that combining use of ZQX-1 with HIF1A signaling inhibitors may further promote the photocytotoxicity of the prodrug.
Immune Response in Cystic Fibrosis: Interplay between the Host and Microbes
Authors: Boutin Sébastien , Guillot Loïc
Published: April 2023

Cystic fibrosis (CF) is a rare genetic disease caused by genetic variants of the cystic fibrosis transmembrane conductance regulator (CFTR) [...]
Sustainable Solvent-Free Selective Oxidation of Benzyl Alcohol Using Ru(0) Supported on Alumina
Authors: Aneggi Eleonora , Campagnolo Filippo , Zuccaccia Daniele , Baratta Walter , Llorca Jordi , Trovarelli Alessandro
Published: April 2023

The selective oxidation of primary alcohols into their corresponding carbonyl compounds is challenging because of the easy over oxidization to acids and esters. The traditional reaction requires large amounts of solvent and oxidant, causing serious environmental issues. Recently, several efforts have been made to transform the reaction into a more sustainable process. Here, we investigated the solvent-free oxidation of benzyl alcohol using air as a green oxidant in the presence of ruthenium supported on alumina and zirconia, thereby meeting atom economy and environmental requirements. The materials were extensively characterized and, in addition to their activity, selectivity, and reusability, the environmental sustainability of the process was assessed according to green chemistry metrics. XRD, TEM, and XPS analyses suggest that the formation of metallic Ru on the support plays a key role in the catalytic activity. Ru supported on alumina, after a reduction treatment, achieves good activity (62% conversion) and a complete selectivity in a very sustainable process (without a solvent and with air as oxidant), as indicated by the very low E-factor value. The formulation is very stable and maintains high activity after recycling.