bluuebunny/crossref_metadata_2025 huggingface dataset:
“B” Regulatory Subunits of PP2A: Their Roles in Plant Development and Stress Reactions
Authors: Máthé Csaba , Freytag Csongor , Kelemen Adrienn , M-Hamvas Márta , Garda Tamás
Published: March 2023

Protein phosphatase PP2A is an enzyme complex consisting of C (catalytic), A (scaffold) and B (regulatory) subunits. B subunits are a large family of proteins that regulate activity, substrate specificity and subcellular localization of the holoenzyme. Knowledge on the molecular functions of PP2A in plants is less than for protein kinases, but it is rapidly increasing. B subunits are responsible for the large diversity of PP2A functioning. This paper intends to give a survey on their multiple regulatory mechanisms. Firstly, we give a short description on our current knowledge in terms of “B”-mediated regulation of metabolic pathways. Next, we present their subcellular localizations, which extend from the nucleus to the cytosol and membrane compartments. The next sections show how B subunits regulate cellular processes from mitotic division to signal transduction pathways, including hormone signaling, and then the emerging evidence for their regulatory (mostly modulatory) roles in both abiotic and biotic stress responses in plants. Knowledge on these issues should be increased in the near future, since it contributes to a better understanding of how plant cells work, it may have agricultural applications, and it may have new insights into how vascular plants including crops face diverse environmental challenges.
Theoretical Study of Hydroxylation of α- and β-Pinene by a Cytochrome P450 Monooxygenase Model
Authors: Shaya Janah , Aloum Lujain , Lu Chung-Shin , Corridon Peter R. , Aoudi Abdulrahman , Shunnar Abeer , Alefishat Eman , Petroianu Georg
Published: March 2023

Previous studies on biocatalytic transformations of pinenes by cytochrome P450 (CYP) enzymes reveal the formation of different oxygenated products from a single substrate due to the multistate reactivity of CYP and the many reactive sites in the pinene scaffold. Up until now, the detailed mechanism of these biocatalytic transformations of pinenes have not been reported. Hereby, we report a systematic theoretical study of the plausible hydrogen abstraction and hydroxylation reactions of α- and β-pinenes by CYP using the density functional theory (DFT) method. All DFT calculations in this study were based on B3LYP/LAN computational methodology using the Gaussian09 software. We used the B3LYP functional with corrections for dispersive forces, BSSE, and anharmonicity to study the mechanism and thermodynamic properties of these reactions using a bare model (without CYP) and a pinene-CYP model. According to the potential energy surface and Boltzmann distribution for radical conformers, the major reaction products of CYP-catalyzed hydrogen abstraction from β-pinene are the doublet trans (53.4%) and doublet cis (46.1%) radical conformer at delta site. The formation of doublet cis/trans hydroxylated products released a total Gibbs free energy of about 48 kcal/mol. As for alpha pinene, the most stable radicals were trans-doublet (86.4%) and cis-doublet (13.6%) at epsilon sites, and their hydroxylation products released a total of ~50 kcal/mol Gibbs free energy. Our results highlight the likely C-H abstraction and oxygen rebounding sites accounting for the multi-state of CYP (doublet, quartet, and sextet spin states) and the formation of different conformers due to the presence of cis/trans allylic hydrogen in α-pinene and β-pinene molecules.
Pathophysiology and Management of Glycemic Alterations before and after Surgery for Pheochromocytoma and Paraganglioma
Authors: Lopez Chiara , Bima Chiara , Bollati Martina , Bioletto Fabio , Procopio Matteo , Arata Stefano , Candela Daniele Giuseppe , Beccuti Guglielmo , Ghigo Ezio , Maccario Mauro , Parasiliti-Caprino Mirko
Published: March 2023

Glycemic alterations are frequent in patients with pheochromocytoma and paraganglioma (PPGL), but the real incidence of secondary diabetes mellitus (DM) is uncertain, because prospective multicenter studies on this topic are lacking in the literature. The main pathophysiological mechanisms of glucose homeostasis alterations in PPGL, related to catecholamine hypersecretion, are impaired insulin and glucagon-like peptide type 1 (GLP-1) secretion and increased insulin resistance. Moreover, it has been reported that different pathways leading to glucose intolerance may be related to the secretory phenotype of the chromaffin tumor. Predictive factors for the development of glucose intolerance in PPGL patients are a higher age at diagnosis, the need for a higher number of anti-hypertensive drugs, and the presence of secreting neoplasms. Tumor resection is strongly related to the resolution of DM in PPGL patients, with a significant improvement of glycemic control in most cases. We can hypothesize a different personalized therapeutic approach based on the secretory phenotype. The adrenergic phenotype is more closely related to reduced insulin secretion, so insulin therapy may be required. On the other hand, the noradrenergic phenotype mainly acts by increasing insulin resistance and, therefore, insulin-sensitizing antidiabetic agents can find a greater application. Regarding GLP-1 receptor agonists, the data suggest a possible promising therapeutic effect, based on the assumption that GLP-1 secretion is impaired in patients with PPGL. The principal predictors of remission of glycemic alterations after surgery for PPGL are a lower preoperative body mass index (BMI), a larger tumor, higher preoperative catecholamine levels, and a shorter duration of the disease (under three years). Otherwise, after resection of PPGL, hypoglycemia can occur as the result of an excessive rebound of preoperative hyperinsulinemia. It is a rare, but potentially severe complication reported in a lot of case reports and a few small retrospective studies. Higher 24-h urinary metanephrine levels, longer operative times and larger tumors are predictive factors for hypoglycemia in this setting. In conclusion, alterations of carbohydrate metabolism are clinically relevant manifestations of PPGL before and after surgery, but there is the need to conduct multicenter prospective studies to obtain an adequate sample size, and to allow the creation of shared strategies for the clinical management of these potentially severe manifestations of PPGL.
Early Pregnancy Regulates Expression of IkappaB Family in Ovine Spleen and Lymph Nodes
Authors: Fang Shengya , Cai Chunjiang , Bai Ying , Zhang Leying , Yang Ling
Published: March 2023

Early pregnancy modulates the maternal immune system, including the spleen and lymph nodes, which participate in maternal innate and adaptive immune responses. Methods: Ovine spleens and lymph nodes were sampled at day 16 of the estrous cycle, and at days 13, 16 and 25 of gestation, and qRT-PCR, Western blot and immunohistochemistry analysis were used to analyze the expression of the IκB family, including BCL-3, IκBα, IκBβ, IκBε, IKKγ, IκBNS and IκBζ. Early pregnancy induced expression of BCL-3, IκBα, IκBε, IKKγ and IκBζ, and expression of BCL-3, IκBβ and IκBNS peaked at day 16 of pregnancy in the spleen. However, early pregnancy suppressed the expression of BCL-3 and IκBNS, but stimulated the expression of IκBβ and IκBζ, and expression levels of IκBα, IκBβ, IκBε and IKKγ peaked in lymph nodes at days 13 and/or 16 of pregnancy. Early pregnancy changed the expression of the IκB family in the maternal spleen and lymph node in a tissue-specific manner, suggesting that the modulation of the IκB family may be involved in regulation of maternal functions of the spleen and lymph nodes, which are necessary for the establishment of maternal immune tolerance during early pregnancy in sheep.
Exosome-Based Liquid Biopsy Approaches in Bone and Soft Tissue Sarcomas: Review of the Literature, Prospectives, and Hopes for Clinical Application
Authors: Agnoletto Chiara , Pignochino Ymera , Caruso Chiara , Garofalo Cecilia
Published: March 2023

The knowledge of exosome impact on sarcoma development and progression has been implemented in preclinical studies thanks to technological advances in exosome isolation. Moreover, the clinical relevance of liquid biopsy is well established in early diagnosis, prognosis prediction, tumor burden assessment, therapeutic responsiveness, and recurrence monitoring of tumors. In this review, we aimed to comprehensively summarize the existing literature pointing out the clinical relevance of detecting exosomes in liquid biopsy from sarcoma patients. Presently, the clinical utility of liquid biopsy based on exosomes in patients affected by sarcoma is under debate. The present manuscript collects evidence on the clinical impact of exosome detection in circulation of sarcoma patients. The majority of these data are not conclusive and the relevance of liquid biopsy-based approaches in some types of sarcoma is still insufficient. Nevertheless, the utility of circulating exosomes in precision medicine clearly emerged and further validation in larger and homogeneous cohorts of sarcoma patients is clearly needed, requiring collaborative projects between clinicians and translational researchers for these rare cancers.
Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer
Authors: Tribukait Bernhard , Lundgren Per-Olof , Kjellman Anders , Norming Ulf , Nyman Claes R. , Jagarlmundi Kiran , Gustafsson Ove
Published: March 2023

Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988–1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.
PTB Regulates the Metabolic Pathways and Cell Function of Keloid Fibroblasts through Alternative Splicing of PKM
Authors: Huang Rong , Han Rong , Yan Yucheng , Yang Jifan , Dong Guoxuan , Wang Miao , Su Zhiguo , Jiao Hu , Fan Jincai
Published: March 2023

Keloids, benign fibroproliferative cutaneous lesions, are characterized by abnormal growth and reprogramming of the metabolism of keloid fibroblasts (KFb). However, the underlying mechanisms of this kind of metabolic abnormality have not been identified. Our study aimed to investigate the molecules involved in aerobic glycolysis and its exact regulatory mechanisms in KFb. We discovered that polypyrimidine tract binding (PTB) was significantly upregulated in keloid tissues. siRNA silencing of PTB decreased the mRNA levels and protein expression levels of key glycolytic enzymes and corrected the dysregulation of glucose uptake and lactate production. In addition, mechanistic studies demonstrated that PTB promoted a change from pyruvate kinase muscle 1 (PKM1) to PKM2, and silencing PKM2 substantially reduced the PTB-induced increase in the flow of glycolysis. Moreover, PTB and PKM2 could also regulate the key enzymes in the tricarboxylic acid (TCA) cycle. Assays of cell function demonstrated that PTB promoted the proliferation and migration of KFb in vitro, and this phenomenon could be interrupted by PKM2 silencing. In conclusion, our findings indicate that PTB regulates aerobic glycolysis and the cell functions of KFb via alternative splicing of PKM.
Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis
Authors: Lange-Consiglio Anna , Gaspari Giulia , Funghi Federico , Capra Emanuele , Cretich Marina , Frigerio Roberto , Bosi Giampaolo , Cremonesi Fausto
Published: March 2023

Persistent post-breeding induced endometritis (PPBIE) is considered a major cause of subfertility in mares. It consists of persistent or delayed uterine inflammation in susceptible mares. There are many options for the treatment of PPBIE, but in this study, a novel approach aimed at preventing the onset of PPBIE was investigated. Stallion semen was supplemented with extracellular vesicles derived from amniotic mesenchymal stromal cells (AMSC-EVs) at the time of insemination to prevent or limit the development of PPBIE. Before use in mares, a dose–response curve was produced to evaluate the effect of AMSC-EVs on spermatozoa, and an optimal concentration of 400 × 106 EVs with 10 × 106 spermatozoa/mL was identified. At this concentration, sperm mobility parameters were not negatively affected. Sixteen susceptible mares were enrolled and inseminated with semen (n = 8; control group) or with semen supplemented with EVs (n = 8; EV group). The supplementation of AMSC-EVs to semen resulted in a reduction in polymorphonuclear neutrophil (PMN) infiltration as well as intrauterine fluid accumulation (IUF; p < 0.05). There was a significant reduction in intrauterine cytokine levels (p < 0.05) for TNF-α and IL-6 and an increase in anti-inflammatory IL-10 in mares in the EV group, suggesting successful modulation of the post-insemination inflammatory response. This procedure may be useful for mares susceptible to PPBIE.
Pillararenes as Promising Carriers for Drug Delivery
Authors: Zyryanov Grigory V. , Kopchuk Dmitry S. , Kovalev Igor S. , Santra Sougata , Majee Adinath , Ranu Brindaban C.
Published: March 2023

Since their discovery in 2008 by N. Ogoshi and co-authors, pillararenes (PAs) have become popular hosts for molecular recognition and supramolecular chemistry, as well as other practical applications. The most useful property of these fascinating macrocycles is their ability to accommodate reversibly guest molecules of various kinds, including drugs or drug-like molecules, in their highly ordered rigid cavity. The last two features of pillararenes are widely used in various pillararene-based molecular devices and machines, stimuli-responsive supramolecular/host–guest systems, porous/nonporous materials, organic–inorganic hybrid systems, catalysis, and, finally, drug delivery systems. In this review, the most representative and important results on using pillararenes for drug delivery systems for the last decade are presented.
Salt-Tolerant Plants, Halophytes, as Renewable Natural Resources for Cancer Prevention and Treatment: Roles of Phenolics and Flavonoids in Immunomodulation and Suppression of Oxidative Stress towards Cancer Management
Authors: Mohammed Hamdoon A. , Emwas Abdul-Hamid , Khan Riaz A.
Published: March 2023

Halophytes and xerophytes, plants with adequate tolerance to high salinity with strong ability to survive in drought ecosystem, have been recognized for their nutritional and medicinal values owing to their comparatively higher productions of secondary metabolites, primarily the phenolics, and the flavonoids, as compared to the normal vegetation in other climatic regions. Given the consistent increases in desertification around the world, which are associated with increasing salinity, high temperature, and water scarcity, the survival of halophytes due to their secondary metabolic contents has prioritized these plant species, which have now become increasingly important for environmental protection, land reclamation, and food and animal-feed security, with their primary utility in traditional societies as sources of drugs. On the medicinal herbs front, because the fight against cancer is still ongoing, there is an urgent need for development of more efficient, safe, and novel chemotherapeutic agents, than those currently available. The current review describes these plants and their secondary-metabolite-based chemical products as promising candidates for developing newer cancer therapeutics. It further discusses the prophylactic roles of these plants, and their constituents in prevention and management of cancers, through an exploration of their phytochemical and pharmacological properties, with a view on immunomodulation. The important roles of various phenolics and structurally diverse flavonoids as major constituents of the halophytes in suppressing oxidative stress, immunomodulation, and anti-cancer effects are the subject matter of this review and these aspects are outlined in details.
C-Terminal Truncated HBx Facilitates Oncogenesis by Modulating Cell Cycle and Glucose Metabolism in FXR-Deficient Hepatocellular Carcinoma
Authors: Wu Xuejun , Ni Zhengzhong , Song Tiantian , Lv Wenya , Chen Yan , Huang Danmei , Xie Yangmin , Huang Weiyi , Niu Yongdong
Published: March 2023

Farnesoid X receptor (FXR) is a nuclear receptor known to play protective roles in anti-hepatocarcinogenesis and regulation of the basal metabolism of glucose, lipids, and bile acids. FXR expression is low or absent in HBV-associated hepatocarcinogenesis. Full-length HBx and HBx C-terminal truncation are frequently found in clinical HCC samples and play distinct roles in hepatocarcinogenesis by interacting with FXR or FXR signaling. However, the impact of C-terminal truncated HBx on the progression of hepatocarcinogenesis in the absence of FXR is unclear. In this study, we found that one known FXR binding protein, a C-terminal truncated X protein (HBx C40) enhanced obviously and promoted tumor cell proliferation and migration by altering cell cycle distribution and inducing apoptosis in the absence of FXR. HBx C40 enhanced the growth of FXR-deficient tumors in vivo. In addition, RNA-sequencing analysis showed that HBx C40 overexpression could affect energy metabolism. Overexpressed HSPB8 aggravated the metabolic reprogramming induced by down-regulating glucose metabolism-associated hexokinase 2 genes in HBx C40-induced hepatocarcinogenesis. Overall, our study suggests that C-terminal truncated HBx C40 synergizes with FXR deficiency by altering cell cycle distribution as well as disturbing glucose metabolism to promote HCC development.
Mycobacterium vaccae NCTC 11659, a Soil-Derived Bacterium with Stress Resilience Properties, Modulates the Proinflammatory Effects of LPS in Macrophages
Authors: Holbrook Evan M. , Zambrano Cristian A. , Wright Caelan T. O. , Dubé Elizabeth M. , Stewart Jessica R. , Sanders William J. , Frank Matthew G. , MacDonald Andrew S. , Reber Stefan O. , Lowry Christopher A.
Published: March 2023

Inflammatory conditions, including allergic asthma and conditions in which chronic low-grade inflammation is a risk factor, such as stress-related psychiatric disorders, are prevalent and are a significant cause of disability worldwide. Novel approaches for the prevention and treatment of these disorders are needed. One approach is the use of immunoregulatory microorganisms, such as Mycobacterium vaccae NCTC 11659, which have anti-inflammatory, immunoregulatory, and stress-resilience properties. However, little is known about how M. vaccae NCTC 11659 affects specific immune cell targets, including monocytes, which can traffic to peripheral organs and the central nervous system and differentiate into monocyte-derived macrophages that, in turn, can drive inflammation and neuroinflammation. In this study, we investigated the effects of M. vaccae NCTC 11659 and subsequent lipopolysaccharide (LPS) challenge on gene expression in human monocyte-derived macrophages. THP-1 monocytes were differentiated into macrophages, exposed to M. vaccae NCTC 11659 (0, 10, 30, 100, 300 µg/mL), then, 24 h later, challenged with LPS (0, 0.5, 2.5, 250 ng/mL), and assessed for gene expression 24 h following challenge with LPS. Exposure to M. vaccae NCTC 11659 prior to challenge with higher concentrations of LPS (250 ng/mL) polarized human monocyte-derived macrophages with decreased IL12A, IL12B, and IL23A expression relative to IL10 and TGFB1 mRNA expression. These data identify human monocyte-derived macrophages as a direct target of M. vaccae NCTC 11659 and support the development of M. vaccae NCTC 11659 as a potential intervention to prevent stress-induced inflammation and neuroinflammation implicated in the etiology and pathophysiology of inflammatory conditions and stress-related psychiatric disorders.
First-Trimester Screening for HELLP Syndrome—Prediction Model Based on MicroRNA Biomarkers and Maternal Clinical Characteristics
Authors: Hromadnikova Ilona , Kotlabova Katerina , Krofta Ladislav
Published: March 2023

We evaluated the potential of cardiovascular-disease-associated microRNAs for early prediction of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Gene expression profiling of 29 microRNAs was performed on whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time RT-PCR. The retrospective study involved singleton pregnancies of Caucasian descent only diagnosed with HELLP syndrome (n = 14) and 80 normal-term pregnancies. Upregulation of six microRNAs (miR-1-3p, miR-17-5p, miR-143-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) was observed in pregnancies destined to develop HELLP syndrome. The combination of all six microRNAs showed a relatively high accuracy for the early identification of pregnancies destined to develop HELLP syndrome (AUC 0.903, p < 0.001, 78.57% sensitivity, 93.75% specificity, cut-off > 0.1622). It revealed 78.57% of HELLP pregnancies at a 10.0% false-positive rate (FPR). The predictive model for HELLP syndrome based on whole peripheral venous blood microRNA biomarkers was further extended to maternal clinical characteristics, most of which were identified as risk factors for the development of HELLP syndrome (maternal age and BMI values at early stages of gestation, the presence of any kind of autoimmune disease, the necessity to undergo an infertility treatment by assisted reproductive technology, a history of HELLP syndrome and/or pre-eclampsia in a previous gestation, and the presence of trombophilic gene mutations). Then, 85.71% of cases were identified at a 10.0% FPR. When another clinical variable (the positivity of the first-trimester screening for pre-eclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm) was implemented in the HELLP prediction model, the predictive power was increased further to 92.86% at a 10.0% FPR. The model based on the combination of selected cardiovascular-disease-associated microRNAs and maternal clinical characteristics has a very high predictive potential for HELLP syndrome and may be implemented in routine first-trimester screening programs.
Salvia sclarea Essential Oil Chemical Composition and Biological Activities
Authors: Kačániová Miroslava , Vukovic Nenad L. , Čmiková Natália , Galovičová Lucia , Schwarzová Marianna , Šimora Veronika , Kowalczewski Przemysław Łukasz , Kluz Maciej Ireneusz , Puchalski Czeslaw , Bakay Ladislav , Vukic Milena D.
Published: March 2023

Salvia sclarea essential oil (SSEO) has a long tradition in the food, cosmetic, and perfume industries. The present study aimed to analyze the chemical composition of SSEO, its antioxidant activity, antimicrobial activity in vitro and in situ, antibiofilm, and insecticidal activity. Besides that, in this study, we have evaluated the antimicrobial activity of SSEO constituent (E)-caryophyllene and standard antibiotic meropenem. Identification of volatile constituents was performed by using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) techniques. Results obtained indicated that the main constituents of SSEO were linalool acetate (49.1%) and linalool (20.6%), followed by (E)-caryophyllene (5.1%), p-cimene (4.9%), a-terpineol (4.9%), and geranyl acetate (4.4%). Antioxidant activity was determined as low by the means of neutralization of the DDPH radical and ABTS radical cation. The SSEO was able to neutralize the DPPH radical to an extent of 11.76 ± 1.34%, while its ability to decolorize the ABTS radical cation was determined at 29.70 ± 1.45%. Preliminary results of antimicrobial activity were obtained with the disc diffusion method, while further results were obtained by broth microdilution and the vapor phase method. Overall, the results of antimicrobial testing of SSEO, (E)-caryophyllene, and meropenem, were moderate. However, the lowest MIC values, determined in the range of 0.22–0.75 µg/mL for MIC50 and 0.39–0.89 µg/mL for MIC90, were observed for (E)-caryophyllene. The antimicrobial activity of the vapor phase of SSEO (towards microorganisms growing on potato) was significantly stronger than that of the contact application. Biofilm analysis using the MALDI TOF MS Biotyper showed changes in the protein profile of Pseudomonas fluorescens that showed the efficiency of SSEO in inhibiting biofilm formation on stainless-steel and plastic surfaces. The insecticidal potential of SSEO against Oxycarenus lavatera was also demonstrated, and results show that the highest concentration was the most effective, showing insecticidal activity of 66.66%. The results obtained in this study indicate the potential application of SSEO as a biofilm control agent, in the shelf-life extension and storage of potatoes, and as an insecticidal agent.
Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs
Authors: Zhao Lan , Wang Shuyuan , Ilves Marit , Lehtonen Sanna , Saikko Leena , El-Nezami Hani , Alenius Harri , Karisola Piia
Published: March 2023

Consumers and manufacturers are exposed to nanosized zinc oxide (nZnO) and silver particles (nAg) via airways, but their biological effects are still not fully elucidated. To understand the immune effects, we exposed mice to 2, 10, or 50 μg of nZnO or nAg by oropharyngeal aspiration and analyzed the global gene expression profiles and immunopathological changes in the lungs after 1, 7, or 28 days. Our results show that the kinetics of responses varied in the lungs. Exposure to nZnO resulted in the highest accumulation of F4/80- and CD3-positive cells, and the largest number of differentially expressed genes (DEGs) were identified after day 1, while exposure to nAg caused peak responses at day 7. Additionally, nZnO mainly activated the innate immune responses leading to acute inflammation, whereas the nAg activated both innate and adaptive immune pathways, with long-lasting effects. This kinetic-profiling study provides an important data source to understand the cellular and molecular processes underlying nZnO- and nAg-induced transcriptomic changes, which lead to the characterization of the corresponding biological and toxicological effects of nZnO and nAg in the lungs. These findings could improve science-based hazard and risk assessment and the development of safe applications of engineered nanomaterials (ENMs), e.g., in biomedical applications.
Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art
Authors: Zhang Han , Cai Jiayou , Yu Siqi , Sun Bin , Zhang Weicheng
Published: March 2023

Eukaryotic elongation factor 1A (eEF1A) canonically delivers amino acyl tRNA to the ribosomal A site during the elongation stage of protein biosynthesis. Yet paradoxically, the oncogenic nature of this instrumental protein has long been recognized. Consistently, eEF1A has proven to be targeted by a wide assortment of small molecules with excellent anticancer activity, among which plitidepsin has been granted approval for the treatment of multiple myeloma. Meanwhile, metarrestin is currently under clinical development for metastatic cancers. Bearing these exciting advances in mind, it would be desirable to present a systematic up-to-date account of the title topic, which, to the best of our knowledge, has thus far been unavailable in the literature. The present review summarizes recent advances in eEF1A-targeting anticancer agents, both naturally occurring and synthetically crafted, with regard to their discovery or design, target identification, structure–activity relationship, and mode of action. Their structural diversity and differential eEF1A-targeting mechanisms warrant continuing research in pursuit of curing eEF1A-driven malignancy.
Human Digital Twin for Personalized Elderly Type 2 Diabetes Management
Authors: Thamotharan Padmapritha , Srinivasan Seshadhri , Kesavadev Jothydev , Krishnan Gopika , Mohan Viswanathan , Seshadhri Subathra , Bekiroglu Korkut , Toffanin Chiara
Published: March 2023

Managing Elderly type 2 diabetes (E-T2D) is challenging due to geriatric conditions (e.g., co-morbidity, multiple drug intake, etc.), and personalization becomes paramount for precision medicine. This paper presents a human digital twin (HDT) framework to manage E-T2D that exploits various patient-specific data and builds a suite of models exploiting the data for prediction and management to personalize diabetes treatment in E-T2D patients. These models include mathematical and deep-learning ones that capture different patient aspects. Consequently, the HDT virtualizes the patient from different viewpoints using an HDT that mimics the patient and has interfaces to update the virtual models simultaneously from measurements. Using these models the HDT obtains deeper insights about the patient. Further, an adaptive patient model fusing this information and a learning-based model predictive control (LB-MPC) algorithm are proposed. The geriatric conditions are captured as model parameters and constraints while solving the LB-MPC to personalize the insulin infusion for E-T2D management. The HDT is deployed on and illustrated with 15 patients using clinical trials and simulations. Our results show that HDT helps improve the time-in-range from 3–75% to 86–97% and reduces insulin infusion by 14–29%.
Attitudes of Anesthesiologists toward Artificial Intelligence in Anesthesia: A Multicenter, Mixed Qualitative–Quantitative Study
Authors: Henckert David , Malorgio Amos , Schweiger Giovanna , Raimann Florian J. , Piekarski Florian , Zacharowski Kai , Hottenrott Sebastian , Meybohm Patrick , Tscholl David W. , Spahn Donat R. , Roche Tadzio R.
Published: March 2023

Artificial intelligence (AI) is predicted to play an increasingly important role in perioperative medicine in the very near future. However, little is known about what anesthesiologists know and think about AI in this context. This is important because the successful introduction of new technologies depends on the understanding and cooperation of end users. We sought to investigate how much anesthesiologists know about AI and what they think about the introduction of AI-based technologies into the clinical setting. In order to better understand what anesthesiologists think of AI, we recruited 21 anesthesiologists from 2 university hospitals for face-to-face structured interviews. The interview transcripts were subdivided sentence-by-sentence into discrete statements, and statements were then grouped into key themes. Subsequently, a survey of closed questions based on these themes was sent to 70 anesthesiologists from 3 university hospitals for rating. In the interviews, the base level of knowledge of AI was good at 86 of 90 statements (96%), although awareness of the potential applications of AI in anesthesia was poor at only 7 of 42 statements (17%). Regarding the implementation of AI in anesthesia, statements were split roughly evenly between pros (46 of 105, 44%) and cons (59 of 105, 56%). Interviewees considered that AI could usefully be used in diverse tasks such as risk stratification, the prediction of vital sign changes, or as a treatment guide. The validity of these themes was probed in a follow-up survey of 70 anesthesiologists with a response rate of 70%, which confirmed an overall positive view of AI in this group. Anesthesiologists hold a range of opinions, both positive and negative, regarding the application of AI in their field of work. Survey-based studies do not always uncover the full breadth of nuance of opinion amongst clinicians. Engagement with specific concerns, both technical and ethical, will prove important as this technology moves from research to the clinic.
Bone Cement and Its Anesthetic Complications: A Narrative Review
Authors: Al-Husinat Lou’i , Jouryyeh Basil , Al Sharie Sarah , Al Modanat Zaid , Jurieh Ahmad , Al Hseinat Laith , Varrassi Giustino
Published: March 2023

The concept of bone cement implantation syndrome (BCIS) is not yet fully understood. In patients undergoing cemented hip arthroplasty, it is a significant factor in intraoperative mortality and morbidity. It may also manifest in a milder form postoperatively, resulting in hypoxia and confusion. In the older population, hip replacement surgery is becoming more prevalent. The risks of elderly patients suffering BCIS may be increased due to co-existing conditions. In this article, we present a narrative review of BCIS including its definition, incidence, risk factors, etiology, pathophysiology, clinical features, prevention, and management, all from an anesthetic point of view.
Ultrasound Doppler Flow Parameters Are Independently Associated with Renal Cortex Contrast-Enhanced Multidetector Computed Tomography Perfusion and Kidney Function
Authors: Lubas Arkadiusz , Zegadło Arkadiusz , Frankowska Emilia , Klimkiewicz Jakub , Jędrych Ewelina , Niemczyk Stanisław
Published: March 2023

Background: The assessment of kidney perfusion has an emerging significance in many diagnostic applications. However, whether and which of the ultrasound Doppler parameters better express renal cortical perfusion (RCP) was not shown. The study aimed to prove the usefulness of Doppler ultrasound parameters in the assessment of RCP regarding low-dose contrast-enhanced multidetector computer tomography (CE-MDCT) blood flow. Methods: Thirty non-stenotic kidneys in twenty-five hypertensive patients (age 58.9 ± 19.0) with mild-to-severe renal dysfunction were included in the study. Resistive index (RI) and end-diastolic velocity (EDV) in segmental arteries, color Doppler dynamic RCP intensity (dRCP), RI (dRI), pulsatility index (dPI), and CE-MDCT blood flow (CBF) in the renal cortex were estimated. Results: CBF correlated significantly with age, estimated glomerular filtration rate (eGFR), RI, EDV, dRI, dPI, and dRCP. In separate multivariable backward regression analyses, RI (R2 = 0.290, p = 0.003) and dRCP (R2 = 0.320, p = 0.001) were independently associated with CBF. However, in the common ultrasound model, only dRCP was independently related to CBF (R2 = 0.317, p = 0.001). Only CBF and EDV were independently associated with eGFR (R2 = 0.510, p < 0.001). Conclusions: Renal cortical perfusion intensity is the best ultrasound marker expressing renal cortical perfusion. In patients with hypertension and kidney dysfunction, renal resistive index and end-diastolic velocity express renal cortical perfusion and kidney function, respectively.
ReUse: REgressive Unet for Carbon Storage and Above-Ground Biomass Estimation
Authors: Pascarella Antonio Elia , Giacco Giovanni , Rigiroli Mattia , Marrone Stefano , Sansone Carlo
Published: March 2023

The United Nations Framework Convention on Climate Change (UNFCCC) has recently established the Reducing Emissions from Deforestation and forest Degradation (REDD+) program, which requires countries to report their carbon emissions and sink estimates through national greenhouse gas inventories (NGHGI). Thus, developing automatic systems capable of estimating the carbon absorbed by forests without in situ observation becomes essential. To support this critical need, in this work, we introduce ReUse, a simple but effective deep learning approach to estimate the carbon absorbed by forest areas based on remote sensing. The proposed method’s novelty is in using the public above-ground biomass (AGB) data from the European Space Agency’s Climate Change Initiative Biomass project as ground truth to estimate the carbon sequestration capacity of any portion of land on Earth using Sentinel-2 images and a pixel-wise regressive UNet. The approach has been compared with two literature proposals using a private dataset and human-engineered features. The results show a more remarkable generalization ability of the proposed approach, with a decrease in Mean Absolute Error and Root Mean Square Error over the runner-up of 16.9 and 14.3 in the area of Vietnam, 4.7 and 5.1 in the area of Myanmar, 8.0 and 1.4 in the area of Central Europe, respectively. As a case study, we also report an analysis made for the Astroni area, a World Wildlife Fund (WWF) natural reserve struck by a large fire, producing predictions consistent with values found by experts in the field after in situ investigations. These results further support the use of such an approach for the early detection of AGB variations in urban and rural areas.
Autonomous Trajectory Tracking Integrated Control of Unmanned Surface Vessel
Authors: Peng Yu , Li Yun
Published: March 2023

Trajectory tracking control of unmanned surface vessels (USVs) has become a popular topic. Regarding the problem of ship collision avoidance encountered in trajectory tracking, more attention needs to be paid to the algorithm application, namely the characteristics of flexibility and accessibility. Thus, a fusion framework of field theoretical planning and a model predictive control (MPC) algorithm is proposed in this paper to obtain a realizable collision-free tracking trajectory, where the trajectory smoothness and collision avoidance constraints under a complex environment need to be considered. Through the designed fast matching (FM) method based on the electric field model, the algorithm gains the direction trend of collision avoidance planning and then combines it with a flexible distance to reconstruct the architecture of the MPC and constraint system, generating the optimal trajectory tracking controller. The new algorithm was tested and validated for several situations, and it can potentially be developed to advance collision-free trajectory tracking navigation in multivessel situations.
Cuproptosis Depicts Immunophenotype and Predicts Immunotherapy Response in Lung Adenocarcinoma
Authors: Zhou Wolong , Cheng Yuanda , Li Linfeng , Zhang Heng , Li Xizhe , Chang Ruimin , Xiao Xiaoxiong , Lu Liqing , Yi Bin , Gao Yang , Zhang Chunfang , Zhang Junjie
Published: March 2023

Background: Although significant progress has been made in immunotherapy for lung adenocarcinoma (LUAD), there is an urgent need to identify effective indicators to screen patients who are suitable for immunotherapy. Systematically investigating the cuproptosis-related genes (CRGs) in LUAD may provide new ideas for patients’ immunotherapy stratification. Method: We comprehensively analyzed the landscape of 12 CRGs in a merged TCGA and GEO LUAD cohort. We investigated the associations between tumor microenvironment and immunophenotypes. We utilized a risk score to predict the prognosis and immunotherapy response for an individual patient. Additionally, we conducted CCK-8 experiments to evaluate the impact of DLGAP5 knockdown on A549 cell proliferation. Result: We utilized an integrative approach to analyze 12 CRGs and differentially expressed genes (DEGs) in LUAD samples, resulting in the identification of two distinct CRG clusters and two gene clusters. Based on these clusters, we generated immunophenotypes and observed that the inflamed phenotype had the most abundant immune infiltrations, while the desert phenotype showed the poorest immune infiltrations. We then developed a risk score model for individual patient prognosis and immunotherapy response prediction. Patients in the low-risk group had higher immune scores and ESTIMATE scores, indicating an active immune state with richer immune cell infiltrations and higher expression of immune checkpoint genes. Moreover, the low-risk group exhibited better immunotherapy response according to IPS, TIDE scores, and Imvigor210 cohort validation results. In addition, our in vitro wet experiments demonstrated that DLGAP5 knockdown could suppress the cell proliferation of A549. Conclusion: Novel cuproptosis molecular patterns reflected the distinct immunophenotypes in LUAD patients. The risk model might pave the way to stratify patients suitable for immunotherapy and predict immunotherapy response.
Combatting Environmental Crisis: Green Orientation in the Sri Lanka Navy
Authors: Iddagoda Anuradha , Manta Otilia , Dissanayake Hiranya , Abeysinghe Rohitha , Perera Dinoka
Published: March 2023

The military’s ongoing efforts to protect the environment are clearly visible. The aim of this study is to bridge an empirical gap, i.e., there is no mediating effect of employee engagement on the relationship between green orientation and employee job performance in the Sri Lanka military context. Employee engagement is the employee’s head, heart and hand involvement in their job as well as their organization. Employee job performance is a main consequence of employee engagement. Because of this consequence, employee engagement has grabbed attention in both the business context and the military context. This quantitative study was achieved through objectives, namely, to identify the impact of green orientation on employee engagement, to identify the impact of employee engagement on employee job performance, and to identify the mediating effect of employee engagement on the relationship between green orientation and employee job performance. The unit of analysis is individual, i.e., officers in the Sri Lanka Navy. The sample size is 243. A cross-sectional study was done in a non-contrived environment with minimum researcher interference. Findings of this study suggest the direct relationship of green orientation and employee engagement, as well as the mediation effect of employee engagement on this relationship.
Urban-Rural Revitalization Space for Sustainable Social Value: An Evaluation in Redesigning Built Environment in Taiwan
Authors: Tsai YuLing , Dewancker Bart Julien , Ardhyanto Athina
Published: March 2023

With the rapid development of globalization, industrialization, urbanization, and informatization, numerous economic activities are aggregated in cities, resulting in uneven resources distribution between urban and rural areas. Additionally, the falling fertility rate has led to the existence of many abandoned education-related architectures in both areas. When an architectural space is non-operational, it delivers neither the fundamental spatial value nor contributes any interaction to its neighbors. This research conducts two educational architecture analyses with respect to their redesign programs in order to evaluate the relation between space and local community. Also, the spatial hierarchy, scale, and characteristics of locality are further investigated in the hope of gaining a deeper understanding of how different revitalization approaches might lead to diverse interaction patterns in the areas. This study shows that different spatial characteristics can affect how people perceive the public space and the way they interact with it. In addition, an effective redesign progress should enhance both space utilization and human-environmental interactions since it can not only promote regional development but also the overall environment sustainability. Thus, an abandoned architecture can be a potential element to invigorate the local community either economically or emotionally.
Achieving Sustainable Development Goals in Ghana: The Contribution of Non-Timber Forest Products towards Economic Development in the Eastern Region
Authors: Akomaning Yaw Okyere , Darkwah Samuel Antwi , Živělová Iva , Hlaváčková Petra
Published: March 2023

Globally, non-timber forest products (NTFPs) continue to contribute vastly to addressing the food, poverty reduction, income, and livelihood requirements of people in rural areas. However, as of now, there are no specific existing data highlighting the periodic contributions of NTFPs to the economy of the eastern region and the country. In Ghana, insufficient attention has been paid to the legislative and regulatory environments for the creation of NTFPs. Since forest policies continue to classify NTFPs as “minor” forest products, they receive less attention than wood in forest management initiatives and policies. The absence of a definitive policy on NTFPs has hampered their promotion, commercialization, and supply chain management. This study analyses the contribution of NTFPs towards economic development in the eastern region and the achievement of SDGs in Ghana. Through focus group discussions and a thematic analysis, it was concluded that NTFPs contribute immensely towards the economic development of the eastern region and the country through employment and direct taxes. Ultimately, it is evident from the study that the destruction of the Atiwa Forest Reserve for the purpose of bauxite mining will widely hinder the country’s achievement of its SDGs. Additionally, the study found that residents will continue to exploit forest resources if the core concerns of institutional deficiencies and rural poverty are not addressed. To curb this situation, there should be the sustainable, regulated, and authorized harvesting of NTFPs/NWFPs, community/user empowerment, and sectoral education and training programmes, etc. Even though these are common solutions, the study found them extremely rare within the study area.
Resilience Practices Contribution Enabling European Landscape Policy Innovation and Implementation
Authors: Colucci Angela
Published: March 2023

The paper is rooted in the results of the Resilience Practices Observatory (RPO) project, which engaged more than one hundred community-led practices to improve local resilience capacities and about fifty applied research and institutional-led initiatives. The article in retracing the complex and articulated RPO research-action project aims to stimulate the disciplinary debate on the contribution and role of resilience practices in a renewed landscape planning framework process. In particular, the paper focuses on the resilience practices acting on ecological landscape enhancement, assuming nature-based solutions as an umbrella concept under numerous approaches, models, and theoretical frameworks supporting the integration of ecological values in the territorial and urban transformation towards their conservation and improvement. The selected cases are placed in the Milano metropolitan area, aiming to safeguard, improve, and valorize urban and periurban landscapes. The cases are used to explore three emerging phenomena: (1) the alliances and the role of community in orienting landscape planning; (2) the role of practices in solution co-design and planning implementation; (3) the role of community in micro-intervention for urban biodiversity and landscape functionality. The final section emphasizes the potential role of community-led initiatives in implementing the NBS European policy and landscape planning guidelines. In the meantime, final remarks underline perspectives in overcoming the existing criticalities towards renovated and adaptive governance process, enabling a more collaborative arena supporting the engagement of differentiated actors along the whole process, from decision making to the implementation and management of landscape planning.