bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands
Authors: Sacco Francesca , Tarchi Matteo , Ferraro Giarita , Merlino Antonello , Facchetti Giorgio , Rimoldi Isabella , Messori Luigi , Massai Lara
Published: September 2021

Three novel platinum(II) complexes bearing N-heterocyclic ligands, i.e., Pt2c, Pt-IV and Pt-VIII, were previously prepared and characterized. They manifested promising in vitro anticancer properties associated with non-conventional modes of action. To gain further mechanistic insight, we have explored here the reactions of these Pt compounds with a few model proteins, i.e., hen egg white lysozyme (HEWL), bovine pancreatic ribonuclease (RNase A), horse heart cytochrome c (Cyt-c) and human serum albumin (HSA), primarily through ESI MS analysis. Characteristic and variegate patterns of reactivity were highlighted in the various cases that appear to depend both on the nature of the Pt complex and of the interacting protein. The protein-bound Pt fragments were identified. In the case of the complex Pt2c, the adducts formed upon reaction with HEWL and RNase A were further characterized by solving the respective crystal structures: this allowed us to determine the exact location of the various Pt binding sites. The implications of the obtained results are discussed in relation to the possible mechanisms of action of these innovative anticancer Pt complexes.
Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders
Authors: Alatibi Khaled I. , Tholen Stefan , Wehbe Zeinab , Hagenbuchner Judith , Karall Daniela , Ausserlechner Michael J. , Schilling Oliver , Grünert Sarah C. , Vockley Jerry , Tucci Sara
Published: September 2021

Medium-chain fatty acids (mc-FAs) are currently applied in the treatment of long-chain fatty acid oxidation disorders (lc-FAOD) characterized by impaired β-oxidation. Here, we performed lipidomic and proteomic analysis in fibroblasts from patients with very long-chain acyl-CoA dehydrogenase (VLCADD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) deficiencies after incubation with heptanoate (C7) and octanoate (C8). Defects of β-oxidation induced striking proteomic alterations, whereas the effect of treatment with mc-FAs was minor. However, mc-FAs induced a remodeling of complex lipids. Especially C7 appeared to act protectively by restoring sphingolipid biosynthesis flux and improving the observed dysregulation of protein homeostasis in LCHADD under control conditions.
Vitamin D and COVID-19: An Overview of Recent Evidence
Authors: Ghelani Drishti , Alesi Simon , Mousa Aya
Published: September 2021

The novel coronavirus severe acute respiratory syndrome (SARS-CoV-2) has progressed rapidly from an outbreak to a global pandemic, with new variants rapidly emerging. Coronavirus disease 2019 (COVID-19), the disease resulting from SARS-CoV-2 infection, can lead to multiorgan damage. Due to the extremely contagious and fatal nature of the virus, it has been a priority of medical research to find effective means of treatment. Amid this search, the role of vitamin D in modulating various aspects of the innate and adaptive immune system has been discussed. This review aims to consolidate the research surrounding the role of vitamin D in the treatment and prevention of COVID-19. While there are some conflicting results reported, the consensus is that vitamin D has a host of immunomodulatory effects which may be beneficial in the context of COVID-19 and that low levels of vitamin D can result in dysfunction of crucial antimicrobial effects, potentially contributing to poor prognosis. Studies also show that the effects of low vitamin D can be mitigated via supplementation, although the benefits of vitamin D supplementation in the treatment of COVID-19 remain controversial.
Alpha-1 Antitrypsin and Hepatocellular Carcinoma in Liver Cirrhosis: SERPINA1 MZ or MS Genotype Carriage Decreases the Risk
Authors: Rabekova Zuzana , Frankova Sona , Jirsa Milan , Neroldova Magdalena , Lunova Mariia , Fabian Ondrej , Kveton Martin , Varys David , Chmelova Klara , Adamkova Vera , Hubacek Jaroslav A. , Spicak Julius , Merta Dusan , Sperl Jan
Published: September 2021

Heterozygotes for Z or S alleles of alpha-1-antrypsin (AAT) have low serum AAT levels. Our aim was to compare the risk of hepatocellular carcinoma (HCC) in patients with liver cirrhosis carrying the SERPINA1 MM, MZ and MS genotypes. The study groups consisted of 1119 patients with liver cirrhosis of various aetiologies, and 3240 healthy individuals served as population controls. The MZ genotype was significantly more frequent in the study group (55/1119 vs. 87/3240, p < 0.0001). The MS genotype frequency was comparable in controls (32/119 vs. 101/3240, p = 0.84). MZ and MS heterozygotes had lower serum AAT level than MM homozygotes (medians: 0.90 g/L; 1.40 g/L and 1.67 g/L; p < 0.001 for both). There were significantly fewer patients with HCC in the cirrhosis group among MZ and MS heterozygotes than in MM homozygotes (5/55 and 1/32 respectively, vs. 243/1022, p < 0.01 for both). The risk of HCC was lower in MZ and MS heterozygotes than in MM homozygotes (OR 0.3202; 95% CI 0.1361–0.7719 and OR 0.1522; 95% CI 0.02941–0.7882, respectively). Multivariate analysis of HCC risk factors identified MZ or MS genotype carriage as a protective factor, whereas age, male sex, BMI and viral aetiology of cirrhosis increased HCC risk.
Performance of Polydopamine Complex and Mechanisms in Wound Healing
Authors: Zheng Dantong , Huang Chongxing , Zhu Xuhao , Huang Haohe , Xu Chenglong
Published: September 2021

Polydopamine (PDA) has been gradually applied in wound healing of various types in the last three years. Due to its rich phenol groups and unique structure, it can be combined with a variety of materials to form wound dressings that can be used for chronic infection, tissue repair in vivo and serious wound healing. PDA complex has excellent mechanical properties and self-healing properties, and it is a stable material that can be used for a long period of time. Unlike other dressings, PDA complexes can achieve both photothermal therapy and electro activity. In this paper, wound healing is divided into four stages: antibacterial, anti-inflammatory, cell adhesion and proliferation, and re-epithelialization. Photothermal therapy can improve the bacteriostatic rate and remove reactive oxygen species to inhibit inflammation. Electrical signals can stimulate cell proliferation and directional migration. With low reactive oxygen species (ROS) levels, inflammatory factors are down-regulated and growth factors are up-regulated, forming regular collagen fibers and accelerating wound healing. Finally, five potential development directions are proposed, including increasing drug loading capacity, optimization of drug delivery platforms, improvement of photothermal conversion efficiency, intelligent electroactive materials and combined 3D printing.
Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing on Citrullination, Carbamylation, and Acetylation
Authors: Kwon Eui-Jong , Ju Ji Hyeon
Published: September 2021

Rheumatoid arthritis (RA) is caused by prolonged periodic interactions between genetic, environmental, and immunologic factors. Posttranslational modifications (PTMs) such as citrullination, carbamylation, and acetylation are correlated with the pathogenesis of RA. PTM and cell death mechanisms such as apoptosis, autophagy, NETosis, leukotoxic hypercitrullination (LTH), and necrosis are related to each other and induce autoantigenicity. Certain microbial infections, such as those caused by Porphyromonasgingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella copri, can induce autoantigens in RA. Anti-modified protein antibodies (AMPA) containing anti-citrullinated protein/peptide antibodies (ACPAs), anti-carbamylated protein (anti-CarP) antibodies, and anti-acetylated protein antibodies (AAPAs) play a role in pathogenesis as well as in prediction, diagnosis, and prognosis. Interestingly, smoking is correlated with both PTMs and AMPAs in the development of RA. However, there is lack of evidence that smoking induces the generation of AMPAs.
In Silico Modeling of the Influence of Environment on Amyloid Folding Using FOD-M Model
Authors: Roterman Irena , Stapor Katarzyna , Fabian Piotr , Konieczny Leszek
Published: September 2021

The role of the environment in amyloid formation based on the fuzzy oil drop model (FOD) is discussed here. This model assumes that the hydrophobicity distribution within a globular protein is consistent with a 3D Gaussian (3DG) distribution. Such a distribution is interpreted as the idealized effect of the presence of a polar solvent—water. A chain with a sequence of amino acids (which are bipolar molecules) determined by evolution recreates a micelle-like structure with varying accuracy. The membrane, which is a specific environment with opposite characteristics to the polar aquatic environment, directs the hydrophobic residues towards the surface. The modification of the FOD model to the FOD-M form takes into account the specificity of the cell membrane. It consists in “inverting” the 3DG distribution (complementing the Gaussian distribution), which expresses the exposure of hydrophobic residues on the surface. It turns out that the influence of the environment for any protein (soluble or membrane-anchored) is the result of a consensus factor expressing the participation of the polar environment and the “inverted” environment. The ratio between the proportion of the aqueous and the “reversed” environment turns out to be a characteristic property of a given protein, including amyloid protein in particular. The structure of amyloid proteins has been characterized in the context of prion, intrinsically disordered, and other non-complexing proteins to cover a wider spectrum of molecules with the given characteristics based on the FOD-M model.
Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas
Authors: Armando Federico , Mecocci Samanta , Orlandi Virginia , Porcellato Ilaria , Cappelli Katia , Mechelli Luca , Brachelente Chiara , Pepe Marco , Gialletti Rodolfo , Ghelardi Alessandro , Passeri Benedetta , Razzuoli Elisabetta
Published: September 2021

Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and oncoproteins (EcPV2 E6 and EcPV2 E7) expression. Moreover, immunohistochemical EMT characterization was carried out by analyzing the main epithelial markers (E-cadherin, β-catenin, and pan-cytokeratin AE3/AE1), the main mesenchymal markers (N-cadherin and vimentin), and the main EMT-related transcription factors (TWIST-1, ZEB-1). PCR analysis was positive for EcPV2 in 16 out of 18 samples. EMT was investigated in epSCC positive for EcPV2. The immunohistochemistry results suggested the presence of EMT processes in the neoplastic cells at the tumor invasive front. Moreover, the significant upregulation of RANKL, together with BCATN1, LEF1, and FOSL1 genes, might suggest a canonical Wnt pathway activation, similarly to what is reported in human penile squamous cell carcinomas
Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy
Authors: Bruder-Nascimento Thiago , Kress Taylor C. , Pearson Matthew , Chen Weiqin , Kennard Simone , Belin de Chantemèle Eric J.
Published: September 2021

The adipokine leptin, which is best-known for its role in the control of metabolic function, is also a master regulator of cardiovascular function. While leptin has been approved for the treatment of metabolic disorders in patients with congenital generalized lipodystrophy (CGL), the effects of chronic leptin deficiency and the treatment on vascular contractility remain unknown. Herein, we investigated the effects of leptin deficiency and treatment (0.3 mg/day/7 days) on aortic contractility in male Berardinelli-Seip 2 gene deficient mice (gBscl2-/-, model of CGL) and their wild-type control (gBscl2+/+), as well as in mice with selective deficiency in endothelial leptin receptor (LepREC-/-). Lipodystrophy selectively increased vascular adrenergic contractility via NO-independent mechanisms and induced hypertrophic vascular remodeling. Leptin treatment and Nox1 inhibition blunted adrenergic hypercontractility in gBscl2-/- mice, however, leptin failed to rescue vascular media thickness. Selective deficiency in endothelial leptin receptor did not alter baseline adrenergic contractility but abolished leptin-mediated reduction in adrenergic contractility, supporting the contribution of endothelium-dependent mechanisms. These data reveal a new direct role for endothelial leptin receptors in the control of vascular contractility and homeostasis, and present leptin as a safe therapy for the treatment of vascular disease in CGL.
Integrin β1 Promotes Pancreatic Tumor Growth by Upregulating Kindlin-2 and TGF-β Receptor-2
Authors: Mia Md Saimon , Jarajapu Yagna , Rao Reena , Mathew Sijo
Published: September 2021

The tumor microenvironment plays a critical role in defining the growth and malignancy of solid tumors. Extracellular matrix (ECM) proteins such as collagen, vitronectin, and fibronectin are major components of the tumor microenvironment. Tumor growth-promoting reciprocal interaction between ECM and cytoplasmic proteins is regulated by the cell surface receptors called integrins. This study investigated the mechanism by which integrin β1 promotes pancreatic tumor growth. In MIA PaCa-2 pancreatic cancer cell line, the loss of integrin β1 protein reduced the ability of cells to proliferate in a 3D matrix and compromised the ability to form a focal adhesion complex. Decreased expression of integrin α5 was observed in KO cells, which resulted in impaired cell spreading and adhesion on vitronectin and fibronectin. Reduced expression of the integrin-associated protein, kindlin-2 was also recorded. The downregulation of kindlin-2 decreased the phosphorylation of Smad2/3 by reducing the expression of TGF-β receptor 2. These results unravel a new mechanism of integrin β1 in tumor growth by modifying the expression of kindlin-2 and TGF-β receptor 2 signaling.
Current Development and Application of Anaerobic Glycolytic Enzymes in Urothelial Cancer
Authors: Yang Yi-Fang , Chuang Hao-Wen , Kuo Wei-Ting , Lin Bo-Syuan , Chang Yu-Chan
Published: September 2021

Urothelial cancer is a malignant tumor with metastatic ability and high mortality. Malignant tumors of the urinary system include upper tract urothelial cancer and bladder cancer. In addition to typical genetic alterations and epigenetic modifications, metabolism-related events also occur in urothelial cancer. This metabolic reprogramming includes aberrant expression levels of genes, metabolites, and associated networks and pathways. In this review, we summarize the dysfunctions of glycolytic enzymes in urothelial cancer and discuss the relevant phenotype and signal transduction. Moreover, we describe potential prognostic factors and risks to the survival of clinical cancer patients. More importantly, based on several available databases, we explore relationships between glycolytic enzymes and genetic changes or drug responses in urothelial cancer cells. Current advances in glycolysis-based inhibitors and their combinations are also discussed. Combining all of the evidence, we indicate their potential value for further research in basic science and clinical applications.
Identification of Phosphorylated Calpain 3 in Rat Brain Mitochondria under mPTP Opening
Authors: Baburuna Yulia , Sotnikova Linda , Krestinina Olga
Published: September 2021

The protein phosphorylation of the membrane-bound mitochondrial proteins has become of interest from the point of view of its regulatory role of the function of the respiratory chain, opening of the mitochondrial permeability transition pore (mPTP), and initiation of apoptosis. Earlier, we noticed that upon phosphorylation of proteins in some proteins, the degree of their phosphorylation increases with the opening of mPTP. Two isoforms of myelin basic protein and cyclic nucleotide phosphodiesterase were identified in rat brain non-synaptic mitochondria and it was concluded that they are involved in mPTP regulation. In the present study, using the mass spectrometry method, the phosphorylated protein was identified as Calpain 3 in rat brain non-synaptic mitochondria. In the present study, the phosphoprotein Calpain-3 (p94) (CAPN3) was identified in the rat brain mitochondria as a phosphorylated truncated form of p60–62 kDa by two-dimensional electrophoresis and mass spectrometry. We showed that the calpain inhibitor, calpeptin, was able to suppress the Ca2+ efflux from mitochondria, preventing the opening of mPTP. It was found that phosphorylated truncated CALP3 with a molecular weight of 60–62 contains p-Tyr, which indicates the possible involvement of protein tyrosine phosphatase in this process.
Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects
Authors: Lin Xiao-Min , Shi Xiao-Xiao , Xiong Le , Nie Jun-Hua , Ye Hai-Shan , Du Jin-Zi , Liu Jia
Published: September 2021

Glioblastoma multiforme (GBM) is the most common lethal primary brain malignancy without reliable therapeutic drugs. IL-13Rα2 is frequently expressed in GBMs as a molecular marker. Resveratrol (Res) effectively inhibits GBM cell growth but has not been applied in vivo because of its low brain bioavailability when administered systemically. A sustained-release and GBM-targeting resveratrol form may overcome this therapeutic dilemma. To achieve this goal, encapsulated Res 30 ± 4.8 nm IL-13Rα2-targeting nanoparticles (Pep-PP@Res) were constructed. Ultraviolet spectrophotometry revealed prolonged Res release (about 25%) from Pep-PP@Res in 48 h and fluorescent confocal microscopy showed the prolonged intracellular Res retention time of Pep-PP@Res (>24 h) in comparison with that of free Res (<4 h) and PP@Res (<4 h). MTT and EdU cell proliferation assays showed stronger suppressive effects of Pep-PP@Res on rat C6 GBM cells than that of PP@Res (p = 0.024) and Res (p = 0.009) when used twice for 4 h/day. Pep-PP@Res had little toxic effect on normal rat brain cells. The in vivo anti-glioblastoma effects of Res can be distinctly improved in the form of Pep-PP@Res nanoparticles via activating JNK signaling, upregulating proapoptosis gene expression and, finally, resulting in extensive apoptosis. Pep-PP@Res with sustained release and GBM-targeting properties would be suitable for in vivo management of GBMs.
The Paramount Role of Drosophila melanogaster in the Study of Epigenetics: From Simple Phenotypes to Molecular Dissection and Higher-Order Genome Organization
Authors: Gibert Jean-Michel , Peronnet Frédérique
Published: September 2021

Drosophila melanogaster has played a paramount role in epigenetics, the study of changes in gene function inherited through mitosis or meiosis that are not due to changes in the DNA sequence. By analyzing simple phenotypes, such as the bristle position or cuticle pigmentation, as read-outs of regulatory processes, the identification of mutated genes led to the discovery of major chromatin regulators. These are often conserved in distantly related organisms such as vertebrates or even plants. Many of them deposit, recognize, or erase post-translational modifications on histones (histone marks). Others are members of chromatin remodeling complexes that move, eject, or exchange nucleosomes. We review the role of D. melanogaster research in three epigenetic fields: Heterochromatin formation and maintenance, the repression of transposable elements by piRNAs, and the regulation of gene expression by the antagonistic Polycomb and Trithorax complexes. We then describe how genetic tools available in D. melanogaster allowed to examine the role of histone marks and show that some histone marks are dispensable for gene regulation, whereas others play essential roles. Next, we describe how D. melanogaster has been particularly important in defining chromatin types, higher-order chromatin structures, and their dynamic changes during development. Lastly, we discuss the role of epigenetics in a changing environment.
Video-Oculography-Assisted Head Impulse Test and Caloric Testing for Detecting Stroke in Acute Vertigo Patients via Modified HINTS Plus
Authors: Siepmann Timo , Gruener Cosima , Simon Erik , Sedghi Annahita , Kitzler Hagen H. , Pallesen Lars-Peder , Barlinn Jessica , Reichmann Heinz , Puetz Volker , Barlinn Kristian
Published: September 2021

Background: We assessed whether detection of stroke underlying acute vertigo using HINTS plus (head-impulse test, nystagmus type, test of skew, hearing loss) can be improved by video-oculography for automated head-impulse test (V-HIT) analysis. Methods: We evaluated patients with acute vestibular syndrome (AVS) presenting to the emergency room using HINTS plus and V-HIT-assisted HINTS plus in a randomized sequence followed by cranial MRI and caloric testing. Image-confirmed posterior circulation stroke or vertebrobasilar TIA were the reference standards to calculate diagnostic accuracy. We repeated statistical analysis for a third protocol that was composed post hoc by replacing the head-impulse test with caloric testing in the HINTS plus protocol. Results: We included 30 AVS patients (ages 55.4 ± 17.2 years, 14 females). Of these, 11 (36.7%) had posterior circulation stroke (n = 4) or TIA (n = 7). Acute V-HIT-assisted HINTS plus was feasible and displayed tendentially higher accuracy than conventional HINTS plus (sensitivity: 81.8%, 95% CI 48.2–97.7%; specificity 31.6%, 95% CI 12.6–56.6% vs. sensitivity 72.7%, 95% CI 39.0–94.0%; specificity 36.8%, 95% CI 16.3–61.6%). The new caloric-supported algorithm showed high accuracy (sensitivity 100%, 95% CI 66.4–100%; specificity 66.7%, 95% CI 41–86.7%). Conclusions: Our study provides pilot data on V-HIT-assisted HINTS plus for acute AVS assessment and indicates the diagnostic value of integrated acute caloric testing.
High-Frequency Ultrasound to Assess Activity in Connective Tissue Panniculitis
Authors: Giavedoni Priscila , Podlipnik Sebastian , Fuertes de Vega Irene , Iranzo Pilar , Mascaró José Manuel
Published: September 2021

Determining disease activity from clinical signs in patients with connective tissue panniculitis (CTP) is often challenging but is essential for therapeutic decision making, which largely relies on immunosuppressant treatment. High-frequency ultrasound (HFUS) may be useful in supporting such decisions by accurately determining CTP activity. This study aimed to investigate the accuracy of HFUS in identifying signs of CTP activity or inactivity and assess its usefulness in therapeutic decision making. A prospective cohort study of consecutive patients with biopsy-proven CTP receiving HFUS was conducted in a tertiary university hospital (2016–2020). HFUS was performed at inclusion and at each 3- or 6-month follow-up visit, depending on disease activity. Twenty-three patients with CTP were included, and 134 HFUSs were performed. In 59.7% (80) of the evaluations, the clinical presentation did not show whether CTP was active or not. In these cases, HFUS showed activity in 38.7% (31) and inactivity in 61.3% (49). In 71.25% (57) of the visits, HFUS was the determinant for therapeutic decisions. Further follow-up showed consistent clinical and HFUS responses in all unclear cases after treatment modification. HFUS appears to be a useful adjunct to the clinical examination for CTP to assess activity and make therapeutic decisions.
Mid-Phase Hyperfluorescent Plaques Seen on Indocyanine Green Angiography in Patients with Central Serous Chorioretinopathy
Authors: Bousquet Elodie , Provost Julien , Zola Marta , Spaide Richard F. , Mehanna Chadi , Behar-Cohen Francine
Published: September 2021

(1) Indocyanine green angiography (ICG-A) shows the presence of mid-phase hyperfluorescent area in central serous chorioretinopathy (CSCR). However, their exact meaning remains uncertain. (2) The clinical and multimodal imaging findings of 100 patients (133 eyes) with CSCR, including the enhanced-depth-imaging OCT (EDI-OCT), blue-light fundus autofluorescence (BAF), fluorescein and indocyanine green angiography (FA and ICG-A) findings were reviewed. Mid-phase hyperfluorescent plaques (MPHP) were defined as fairly well circumscribed hyperfluorescent regions during the midphase of the ICG-A. The association between MPHP and other clinical/imaging parameters was assessed using a multiple logistic regression analysis. (3) MPHP were detected in 59.4% of eyes with CSCR. The chronic form of the disease, the presence of irregular pigment epithelium detachments (PED) and the retinal pigment epithelium (RPE) changes seen on FA were associated with the presence of MPHP in the multivariate analysis (p = 0.015; p = 0.018 and p = 0.002; respectively). OCT showed RPE bulges or PED in 98.7% of areas with MPHP and BAF showed changes in 57.3% of areas with MPHP. (4) MPHP were associated with a chronic form of CSCR and colocated with PED or RPE bulges. MPHP should be recognized as a sign of early RPE dysfunction before it is detected with BAF.
Discrepant End-Tidal Concentrations of Sevoflurane at the Same A-Line Autoregressive Index Level during Induction of General Anesthesia: An Observational Study
Authors: Hsu Che-Hao , Ho Shung-Tai , Lu Chih-Cherng , Wang Ju-O , Yeh Te-Chun , Lin Tso-Chou
Published: September 2021

Background: The A-Line Autoregressive Index (AAI), which is derived from auditory evoked potentials, has been used for determining anesthetic depth. This study verified the correlation between AAI values and the corresponding end-tidal concentrations of sevoflurane during general anesthesia induction. Methods: Thirty young male adults undergoing elective minor orthopedic surgery were sequentially allocated to receive inspiratory 3%, 5%, or 6% sevoflurane for mask induction, followed by mechanical ventilation after tracheal intubation. The inspiratory, end-tidal and estimated jugular bulb concentrations of sevoflurane were recorded at three target AAI values: below 20, below 10, and at the start of burst suppression. Results: The mean time to loss of consciousness in the 6% sevoflurane group was shorter than that in the 5% and 3% groups; however, the groups had comparable AAI values (range: 16–45). The 6% group had a higher end-tidal concentration (4.5% ± 0.2% vs. 3.8% ± 0.2%, p < 0.05) than did the 5% group, despite having the same target anesthetic levels by AAI score ≤10, whereas the estimated jugular bulb concentrations were comparable (1.9% vs. 1.9%) in both groups. Conclusions: Following mechanical ventilation with inspiratory 3%, 5%, or 6% sevoflurane, the end-tidal concentrations were discrepant at the same end points of AAI levels, despite similar estimated jugular bulb concentrations of sevoflurane. Thus, conventional alveolar concentration may overestimate anesthesia depth during rapid wash-in of sevoflurane.
Risk Factors for Perioperative Hemodynamic Instability in Pheochromocytoma: A Systematic Review and Meta-Analysis
Authors: Urabe Fumihiko , Kimura Shoji , Iwatani Kosuke , Takahashi Kazuhiro , Ito Kagenori , Tashiro Kojiro , Tsuzuki Shunsuke , Miki Jun , Kimura Takahiro , Furuta Nozomu , Egawa Shin
Published: September 2021

Objective: To evaluate the risk factors of perioperative hemodynamic instability in pheochromocytoma, we conducted a systematic search of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-analysis. Methods: In April 2021, we systematically searched PubMed, the Cochrane library, and Scopus for relevant studies on the risk factors of perioperative hemodynamic instability of adrenalectomy in patients with pheochromocytoma, and we subjected the findings from those studies to formal meta-analysis. Results: Our systematic review identified 14 studies involving 1725 patients, of which nine studies with 967 patients were eligible for meta-analysis. The results of meta-analysis showed that tumor size (odds ratio (OR): 1.14 for each increased cm, 95% confidence interval (CI) 1.03–1.26, z = 2.57) and urinary norepinephrine (OR, 1.51: 95% CI 1.26–1.81; z = 4.50) were most closely associated with the occurrence of perioperative hemodynamic instability. Conclusion: These findings suggest that tumor size and urinary norepinephrine are important predictors and risk factors for perioperative hemodynamic instability in adrenalectomy for pheochromocytoma. Such findings may be of value to surgeons and anesthesiologists when considering or preparing for this procedure.
Extent of Cardiac Damage and Mortality in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Avvedimento Marisa , Franzone Anna , Leone Attilio , Piccolo Raffaele , Castiello Domenico Simone , Ilardi Federica , Mariani Andrea , Esposito Roberta , Iapicca Cristina , Angellotti Domenico , Scalamogna Maria , Santoro Ciro , Di Serafino Luigi , Cirillo Plinio , Esposito Giovanni
Published: September 2021

(1) Aims: We sought to assess the impact of the extent of cardiac damage on survival among real-world patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). (2) Methods: A staging classification was applied to 262 patients from the EffecTAVI Registry at baseline and re-assessed within 30-days after TAVI. The primary endpoint of the study was all-cause mortality at 1-year. Secondary endpoints included cerebrovascular accident, myocardial infarction, permanent pacemaker implantation, endocarditis, and re-hospitalization for all causes. (3) Results: At baseline, 23 (8.7%) patients were in Stage 0/1 (no cardiac damage/left ventricular damage), 106 (40.4%) in Stage 2 (left atrial or mitral valve damage), 59 (22.5%) in Stage 3 (pulmonary vasculature or tricuspid valve damage) and 74 (28.3%) in Stage 4 (right ventricular damage). At 30-days after TAVI, a lower prevalence of advanced stages of cardiac damage than baseline, mainly driven by a significant improvement in left ventricular diastolic parameters and right ventricular function, was reported. At 1-year, a stepwise increase in mortality rates was observed according to staging at baseline: 4.3% in Stage 0/1, 6.6% in Stage 2, 18.6% in Stage 3 and 21.6% in Stage 4 (p = 0.08). No differences were found in secondary endpoints. (4) Conclusions: TAVI has an early beneficial impact on the left ventricular diastolic and right ventricular function. However, the extent of cardiac damage at baseline significantly affects the risk of mortality at 1-year after the procedure.
Intraosseous Venous Malformation of the Zygomatic Bone: Comparison between Virtual Surgical Planning and Standard Surgery with Review of the Literature
Authors: Antúnez-Conde Raúl , Navarro Cuéllar Carlos , Salmerón Escobar José Ignacio , Díez-Montiel Alberto , Navarro Cuéllar Ignacio , Dell’Aversana Orabona Giovanni , del Castillo Pardo de Vera José Luis , Navarro Vila Carlos , Cebrián Carretero José Luis
Published: September 2021

Intraosseous venous malformations affecting the zygomatic bone are infrequent. Primary reconstruction is usually accomplished with calvarial grafts, although the use of virtual surgical planning, cutting guides and patient-specific implants (PSI) have had a major development in recent years. A retrospective study was designed and implemented in patients diagnosed with intraosseous venous malformation during 2006–2021, and a review of the scientific literature was also performed to clarify diagnostic terms. Eight patients were treated, differentiating two groups according to the technique: four patients were treated through standard surgery with resection and primary reconstruction of the defect with calvarial graft, and four patients underwent resection and primary reconstruction through virtual surgical planning (VSP), cutting guides, STL models developed with CAD-CAM technology and PSI (titanium or Polyether-ether-ketone). In the group treated with standard surgery, 75% of the patients developed sequelae or morbidity associated with this technique. The operation time ranged from 175 min to 210 min (average 188.7 min), the length of hospital ranged from 4 days to 6 days (average 4.75 days) and the postoperative CT scan showed a defect surface coverage of 79.75%. The aesthetic results were “excellent” in 25% of the patients, “good” in 50% and “poor” in 25%. In the VSP group, 25% presented sequelae associated with surgical treatment. The operation time ranged from 99 min to 143 min (average 121 min), the length of hospital stay ranged from 1 to 2 days (average of 1.75 days) and 75% of the patients reported “excellent” results. Postoperative CT scan showed 100% coverage of the defect surface in the VSP group. The multi-stage implementation of virtual surgical planning with cutting guides, STL models and patient-specific implants increases the reconstructive accuracy in the treatment of patients diagnosed with intraosseous venous malformation of the zygomatic bone, reducing sequelae, operation time and average hospital stay, providing a better cover of the defect, and improving the precision of the reconstruction and the aesthetic results compared to standard technique.
Toughening of Bioceramic Composites for Bone Regeneration
Authors: Abbas Zahid , Dapporto Massimiliano , Tampieri Anna , Sprio Simone
Published: September 2021

Bioceramics are widely considered as elective materials for the regeneration of bone tissue, due to their compositional mimicry with bone inorganic components. However, they are intrinsically brittle, which limits their capability to sustain multiple biomechanical loads, especially in the case of load-bearing bone districts. In the last decades, intense research has been dedicated to combining processes to enhance both the strength and toughness of bioceramics, leading to bioceramic composite scaffolds. This review summarizes the recent approaches to this purpose, particularly those addressed to limiting the propagation of cracks to prevent the sudden mechanical failure of bioceramic composites.
A Practical Trajectory Tracking Scheme for a Twin-Propeller Twin-Hull Unmanned Surface Vehicle
Authors: Jin Jiucai , Liu Deqing , Wang Dong , Ma Yi
Published: September 2021

Trajectory tracking is a basis of motion control for Unmanned Surface Vehicles (USVs), which has been researched well for common USVs. The twin-propeller and twin-hull USV (TPTH-USV) is a special vehicle for applications due to its good stability and high load. We propose a three-layered architecture of trajectory tracking for the TPTH-USV which explicitly decomposes into trajectory guidance, a motion limitator and controller. The trajectory guidance transforms an expected trajectory into an expected speed and expected course in a kinematic layer. The motion limitator describes some restriction for motion features of the USV in the restriction layer, such as the maximum speed and maximum yaw rate. The controller is to control the speed and course of the USV in the kinetic layer. In the first layer, an adaptive line-of-sight guidance law is designed by regulating the speed and course to track a curved line considering the sideslip angle. In the second layer, the motion features are extracted from an identified speed and course coupled model. In the last layer, the course and speed controller are designed based on a twin-PID controller. The feasibility and practicability of the proposed trajectory tracking scheme is validated in sea experiments by a USV called ‘Jiuhang 490’.
Structural Insight into a Yeast Maltase—The BaAG2 from Blastobotrys adeninivorans with Transglycosylating Activity
Authors: Ernits Karin , Kjeldsen Christian , Persson Karina , Grigor Eliis , Alamäe Tiina , Visnapuu Triinu
Published: September 2021

An early-diverged yeast, Blastobotrys (Arxula) adeninivorans (Ba), has biotechnological potential due to nutritional versatility, temperature tolerance, and production of technologically applicable enzymes. We have biochemically characterized from the Ba type strain (CBS 8244) the GH13-family maltase BaAG2 with efficient transglycosylation activity on maltose. In the current study, transglycosylation of sucrose was studied in detail. The chemical entities of sucrose-derived oligosaccharides were determined using nuclear magnetic resonance. Several potentially prebiotic oligosaccharides with α-1,1, α-1,3, α-1,4, and α-1,6 linkages were disclosed among the products. Trisaccharides isomelezitose, erlose, and theanderose, and disaccharides maltulose and trehalulose were dominant transglycosylation products. To date no structure for yeast maltase has been determined. Structures of the BaAG2 with acarbose and glucose in the active center were solved at 2.12 and 2.13 Å resolution, respectively. BaAG2 exhibited a catalytic domain with a (β/α)8-barrel fold and Asp216, Glu274, and Asp348 as the catalytic triad. The fairly wide active site cleft contained water channels mediating substrate hydrolysis. Next to the substrate-binding pocket an enlarged space for potential binding of transglycosylation acceptors was identified. The involvement of a Glu (Glu309) at subsite +2 and an Arg (Arg233) at subsite +3 in substrate binding was shown for the first time for α-glucosidases.
ε-poly-L-lysine Affects the Vegetative Growth, Pathogenicity and Expression Regulation of Necrotrophic Pathogen Sclerotinia sclerotiorum and Botrytis cinerea
Authors: Zhou Tao , Liu He , Huang Yuanmin , Wang Zehao , Shan Yuhang , Yue Yan , Xia Zihao , Liang Yue , An Mengnan , Wu Yuanhua
Published: September 2021

Microbial secondary metabolites produced by Streptomyces are applied to control plant diseases. The metabolite, ε-poly-L-lysine (ε-PL), is a non-toxic food preservative, but the potential application of this compound as a microbial fungicide in agriculture is rarely reported. In this study, the effect and mode of action of ε-PL on two necrotrophic pathogenic fungi, Sclerotinia sclerotiorum and Botrytis cinerea, were investigated. The results showed that ε-PL effectively inhibited the mycelial growth of S. sclerotiorum and B. cinerea with EC50 values of 283 μg/mL and 281 μg/mL, respectively. In addition, ε-PL at the dose of 150 and 300 μg/mL reduced S. sclerotiorum sclerotia formation. The results of the RNA-seq and RT-qPCR validation indicated that ε-PL significantly regulated the gene expression of critical differential expressed genes (DEGs) involved in fungal growth, metabolism, pathogenicity, and induced an increase in the expression of the fungal stress responses and the detoxification genes. These results provided new insights for understanding the modes of action of ε-PL on S. sclerotiorum and B. cinerea and improved the sustainable management of these plant diseases.
Knockout of Hepatocyte Growth Factor by CRISPR/Cas9 System Induces Apoptosis in Hepatocellular Carcinoma Cells
Authors: Lee Han Ki , Lim Heui Min , Park See-Hyoung , Nam Myeong Jin
Published: September 2021

Background: CRISPR/Cas9 system is a prokaryotic adaptive immune response system that uses noncoding RNAs to guide the Cas9 nuclease to induce site-specific DNA cleavage. Hepatocyte growth factor (HGF) is a well-known growth factor that plays a crucial role in cell growth and organ development. According to recent studies, it has been reported that HGF promoted growth of hepatocellular carcinoma (HCC) cells. Here, we investigated the apoptotic effects in HCC cells. Methods: Crispr-HGF plasmid was constructed using GeneArt CRISPR Nuclease Vector. pMex-HGF plasmid that targets HGF overexpressing gene were designed with pMex-neo plasmid. We performed real time-polymerase chain reaction to measure the expression of HGF mRNA. We performed cell counting assay and colony formation assay to evaluate cell proliferation. We also carried out migration assay and invasion assay to reveal the inhibitory effects of Crispr-HGF in HCC cells. Furthermore, we performed cell cycle analysis to detect transfection of Crispr-HGF induced cell cycle arrest. Collectively, we performed annexin V/PI staining assay and Western blot assay. Results: In Crispr-HGF-transfected group, the mRNA expression levels of HGF were markedly downregulated compared to pMex-HGF-transfected group. Moreover, Crispr-HGF inhibited cell viability in HCC cells. We detected that wound area and invaded cells were suppressed in Crispr-HGF-transfected cells. The results showed that transfection of Crispr-HGF induced cell cycle arrest and apoptosis in HCC cells. Expression of the phosphorylation of mitogen activated protein kinases and c-Met protein was regulated in Crispr-HGF-transfected group. Interestingly, we found that the expression of HGF protein in conditioned media significantly decreased in Crispr-HGF-transfected group. Conclusions: Taken together, we found that inhibition of HGF through transfection of Crispr-HGF suppressed cell proliferation and induced apoptotic effects in HCC Huh7 and Hep3B cells.
Lipid and Energy Metabolism of the Gut Microbiota Is Associated with the Response to Probiotic Bifidobacterium breve Strain for Anxiety and Depressive Symptoms in Schizophrenia
Authors: Yamamura Ryodai , Okubo Ryo , Katsumata Noriko , Odamaki Toshitaka , Hashimoto Naoki , Kusumi Ichiro , Xiao Jinzhong , Matsuoka Yutaka J.
Published: September 2021

A recent meta-analysis found that probiotics have moderate-to-large beneficial effects on depressive symptoms in patients with psychiatric disorders. However, it remains unclear how the baseline gut microbiota before probiotic administration influences the host’s response to probiotics. Therefore, we aimed to determine whether the predicted functional profile of the gut microbiota influences the effectiveness of probiotic treatment in patients with schizophrenia. A total of 29 patients with schizophrenia consumed Bifidobacterium breve A-1 (synonym B. breve MCC1274) for 4 weeks. We considered patients who showed a 25% or more reduction in the Hospital Anxiety and Depression Scale total score at 4 weeks from baseline to be “responders” and those who did not to be “non-responders”. We predicted the gut microbial functional genes based on 16S rRNA gene sequences and applied the linear discriminant analysis effect size method to determine the gut microbial functional genes most likely to explain the differences between responders and non-responders at baseline. The results showed that lipid and energy metabolism was elevated at baseline in responders (n = 12) compared to non-responders (n = 17). These findings highlight the importance of assessing the gut microbial functional genes at baseline before probiotic therapy initiation in patients with psychiatric disorders.
Mid- and Late-Life Migraine Is Associated with an Increased Risk of All-Cause Dementia and Alzheimer’s Disease, but Not Vascular Dementia: A Nationwide Retrospective Cohort Study
Authors: Lee Hyun-Joo , Yu Hyunjae , Gil Myeong Son , Park Kijoon , Kim Dong-Kyu
Published: September 2021

We used a nationwide cohort sample of data from 2002 to 2013, representing approximately 1 million patients to investigate the prospective association between migraine and dementia. The migraine group (n = 1472) included patients diagnosed between 2002 and 2004, aged over 55 years; the comparison group was selected using propensity score matching (n = 5888). Cox proportional hazards regression analyses was used to calculate the hazard ratios (HRs). The incidence of dementia was 13.5 per 1000 person-years in the migraine group. Following adjustment for sociodemographic and comorbidities variables, patients with migraine developed dementia more frequently than those in the comparison group (adjusted HR = 1.37, 95% confidence interval [CI], 1.16–1.61). In the subgroup analysis, we found a higher HR of dementia events in male, the presence of comorbidities, and older age (≥65) patients with migraine, compared to those without migraine. Moreover, patients with migraine had a significantly higher incidence of Alzheimer’s disease (adjusted HR = 1.31, 95% CI, 1.08–1.58), but not vascular dementia, than those without migraine. Therefore, our findings suggest that mid- and late-life migraines may be associated with an increased incidence of all-cause dementia and Alzheimer’s disease, but not vascular dementia.
Leveraging the Power of Online Referral for E-Business: The Moderated Mediation Model
Authors: Chen Chih-Hung
Published: September 2021

This study utilized the Kano model to practically identify the key attributes of online service quality of e-learning education companies. Along with a review of theoretical sources related to service quality, this paper placed similar attributes into the same cluster and finalized four constructs, i.e., reliability, responsiveness, competence, and engagement. In addition, consumer perception plays a mediating role in the relationship between online service quality and online purchase intention, while online customer referral is taken as a moderator indirectly influencing customer perceptions because people like to share their purchasing and usage experiences online. Subsequently, a structured questionnaire was designed and survey data were collected from 418 respondents through various social media. Hypotheses were tested using the structural equation modeling (SEM) and SPSS Process Model 4 and 7. The outcomes show (1) consumer perception significantly mediates the relationship between online service quality and online purchase intention, and (2) online customer referral has a profound effect on consumer perception, indicating that it indirectly affects purchase intention. Online customer referral, therefore, may help e-learning education companies to improve service quality with key features that better positions them to target online learners.