bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Piercing: A Pretty Risk—A Scoping Review of Local and Systemic Complications of This Current Widespread Fashion
Authors: Malcangi Giuseppina , Patano Assunta , Palmieri Giulia , Riccaldo Lilla , Pezzolla Carmela , Mancini Antonio , Inchingolo Alessio Danilo , Di Venere Daniela , Piras Fabio , Inchingolo Francesco , Dipalma Gianna , Inchingolo Angelo Michele
Published: May 2023

Piercing insertion is a common practice among people of all ages for different reasons (e.g., esthetics, culture, religion). In the oral cavity, the jewel can be placed in the lips, cheeks, tongue, and frenulum. The presence of an oral piercing could cause local and systemic complications in the short term. In the long term, irreversible damage may occur to the hard and soft tissues of the oral cavity. Different authors in the past have produced publications focusing on this issue. This study analyzes 10 published articles sourced from online databases according to the PRISMA flowchart. These articles were chosen from the 501 suitable papers initially found. PubMed, Web of Science, and Scopus were used as the online databases for searching for papers that matched the topic, using the keywords “complication” and “oral piercing”. The purpose of this review is to describe and analyze all possible complications related to the presence of a piercing in the mouth. Local and systemic complications are related to the presence of plaque and localized pathogenic micro-organisms that can spread via the bloodstream, although they rarely occur in patients without predisposing conditions. Maintaining proper oral hygiene and frequent check-ups are essential to avoid the onset of complications.
Longitudinal Process of Setting and Achieving Activity- and Participation-Level Goals in Home Rehabilitation in Japan: A Qualitative Study Using Trajectory Equifinality Modeling
Authors: Saito Yuki , Tomori Kounosuke , Sawada Tatsunori , Ohno Kanta
Published: May 2023

This study aimed to clarify the longitudinal goal negotiation and collaboration process of achieving activity- and participation-level goals. We conducted a qualitative study using the trajectory equifinality model. Nine occupational therapists with experience in setting and achieving activity- and participation-level goals were recruited and interviewed about their clients. We identified two phases and four pathways in the setting and attainment process for activity- and participation-level goals. Throughout the longitudinal goal-setting process, when the occupational therapist and client had difficulty discussing activity- and participation-level goals, the therapist respected the client’s expectations, explained the purpose of occupational therapy in detail, and conducted individual face-to-face interviews. When it was difficult to provide work-based interventions, the occupational therapist made flexible use of functional training, elemental movement training, occupation-based practice, and environmental modifications. The results of this study may assist in supporting clients to improve their activity and participation in home rehabilitation.
Impact of Novel Active Layer-by-Layer Edible Coating on the Qualitative and Biochemical Traits of Minimally Processed ‘Annurca Rossa del Sud’ Apple Fruit
Authors: Magri Anna , Rega Pietro , Capriolo Giuseppe , Petriccione Milena
Published: May 2023

The color changes brought on by the enzymatic interactions of phenolic compounds with released endogenous polyphenol oxidase and the penetration of oxygen into the tissue has a significant impact on the commercialization of fresh-cut fruit, such as apples. This process causes a loss of quality in fresh-cut apples, resulting in browning of the fruit surface. By acting as a semipermeable barrier to gases and water vapor and thus lowering respiration, enzymatic browning, and water loss, edible coatings can provide a chance to increase the shelf life of fresh-cut produce. In this study, the effect of edible coatings composed of carboxymethylcellulose (CMC, 1%), sodium alginate (SA, 1%), citric acid (CA, 1%), and oxalic acid (OA, 0.5%) on fresh-cut ‘Annurca Rossa del Sud’ apple was studied. Four formulations of edible coatings, A. SA+CMC, B. SA+CMC+CA, C. SA+CMC+OA, and D. SA+CMC+CA+OA, were tested. Fresh-cut apples were dipped into different solutions and then stored at 4 °C, and physicochemical and biochemical analyses were performed at 0, 4, 8, and 12 days of storage. Results demonstrated that all four combinations improved the shelf-life of fresh-cut apple by slowing down the qualitative postharvest decay, total soluble solid, and titratable acidity. The browning index was highest in the control samples (82%), followed by CMC+SA (53%), CMC+SA+CA (32%), CMC+SA+OA (22%), and finally CMC+SA+CA+OA (7%) after 12 days of cold storage. Furthermore, coating application increased the bioactive compound content and antioxidant enzyme activities. Furthermore, the synergistic activity of SA+CMC+CA+OA reduces enzymatic browning, prolonging the postharvest life of minimally processed ‘Annurca Rossa del Sud’ apples.
The Synthesis and Biological Activity of Organotin Complexes with Thio-Schiff Bases Bearing Phenol Fragments
Authors: Smolyaninov Ivan V. , Poddel’sky Andrey I. , Burmistrova Daria A. , Voronina Yulia K. , Pomortseva Nadezhda P. , Polovinkina Maria A. , Almyasheva Nailya R. , Zamkova Maria A. , Berberova Nadezhda T. , Eremenko Igor L.
Published: May 2023

A number of novel di- and triorganotin(IV) complexes 1–5 (Ph2SnL1, Ph2SnL2, Et2SnL2, Ph3SnL3, Ph3SnL4) with mono- or dianionic forms of thio-Schiff bases containing antioxidant sterically hindered phenol or catechol fragments were synthesized. Compounds 1–5 were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of complexes 1 and 2 in the crystal state were established by single-crystal X-ray analysis. The antioxidant activity of new complexes as radical scavengers was estimated in DPPH and ABTS assays. It was found that compounds 4 and 5 with free phenol or catechol fragments are more active in these tests than complexes 1–3 with tridentate O,N,S-coordinated ligands. The effect of compounds 1–5 on the promoted oxidative damage of the DNA by 2,2’-azobis(2-amidinopropane) dihydrochloride and in the process of rat liver (Wistar) homogenate lipid peroxidation in vitro was determined. Complexes 4 and 5 were characterized by more pronounced antioxidant activity in the reaction of lipid peroxidation in vitro than compounds 1–3. The antiproliferative activity of compounds 1–5 was investigated against MCF-7, HTC-116, and A-549 cell lines by an MTT test. The values of IC50 are significantly affected by the presence of free antioxidant fragments and the coordination site for binding.
The Role of Autotaxin and LPA Signaling in Embryonic Development, Pathophysiology and Cancer
Authors: Magkrioti Christiana , Kaffe Eleanna , Aidinis Vassilis
Published: May 2023

Autotaxin (ATX) or Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) is a secreted enzyme with lysophospholipase D activity, with its primary function being the extracellular hydrolysis of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid [...]
Puerarin Prevents Cadmium-Induced Neuronal Injury by Alleviating Autophagic Dysfunction in Rat Cerebral Cortical Neurons
Authors: Wang Li , Wang Tao , Wen Shuangquan , Song Ruilong , Zou Hui , Gu Jianhong , Liu Xuezhong , Bian Jianchun , Liu Zongping , Yuan Yan
Published: May 2023

Autophagic dysfunction is one of the main mechanisms of cadmium (Cd)-induced neurotoxicity. Puerarin (Pue) is a natural antioxidant extracted from the medicinal and edible homologous plant Pueraria lobata. Studies have shown that Pue has neuroprotective effects in a variety of brain injuries, including Cd-induced neuronal injury. However, the role of Pue in the regulation of autophagy to alleviate Cd-induced injury in rat cerebral cortical neurons remains unclear. This study aimed to elucidate the protective mechanism of Pue in alleviating Cd-induced injury in rat cerebral cortical neurons by targeting autophagy. Our results showed that Pue alleviated Cd-induced injury in rat cerebral cortical neurons in vitro and in vivo. Pue activates autophagy and alleviates Cd-induced autophagic blockade in rat cerebral cortical neurons. Further studies have shown that Pue alleviates the Cd-induced inhibition of autophagosome–lysosome fusion, as well as the inhibition of lysosomal degradation. The specific mechanism is related to Pue alleviating the inhibition of Cd on the expression levels of the key proteins Rab7, VPS41, and SNAP29, which regulate autophagosome–lysosome fusion, as well as the lysosome-related proteins LAMP2, CTSB, and CTSD. In summary, these results indicate that Pue alleviates Cd-induced autophagic dysfunction in rat cerebral cortical neurons by alleviating autophagosome–lysosome fusion dysfunction and lysosomal degradation dysfunction, thereby alleviating Cd-induced neuronal injury.
Structural Characteristics–Reactivity Relationships for Catalytic Depolymerization of Lignin into Aromatic Compounds: A Review
Authors: Wang Xin , Xu Wenbiao , Zhang Dan , Li Xiangyu , Shi Junyou
Published: May 2023

Developing renewable biomass resources is an urgent task to reduce climate change. Lignin, the only renewable aromatic feedstock present in nature, has attracted considerable global interest in its transformation and utilization. However, the complexity of lignin’s structure, uncertain linkages, stability of side chain connection, and inevitable recondensation of reaction fragments make lignin depolymerization into biofuels or platform chemicals a daunting challenge. Therefore, understanding the structural characteristics and reactivity relationships is crucial for achieving high-value utilization of lignin. In this review, we summarize the key achievements in the field of lignin conversion with a focus on the effects of the β-O-4 content, S/G ratio, lignin sources, and an “ideal” lignin—catechyl lignin. We discuss how these characteristics influence the formation of lignin monomer products and provide an outlook on the future direction of lignin depolymerization.
Effective Pre-Clinical Treatment of Fish Envenoming with Polyclonal Antiserum
Authors: Lopes Ferreira Monica , Falcão Maria Alice Pimentel , Bruni Fernanda Miriane , Haddad Vidal , Marques Elineide Eugênio , Seibert Carla Simone , Lima Carla
Published: May 2023

Envenomation by venomous fish, although not always fatal, is capable of causing damage to homeostasis by activating the inflammatory process, with the formation of edema, excruciating pain, necrosis that is difficult to heal, as well as hemodynamic and cardiorespiratory changes. Despite the wide variety of pharmacological treatments used to manage acute symptoms, none are effective in controlling envenomation. Knowing the essential role of neutralizing polyclonal antibodies in the treatment of envenoming for other species, such as snakes, this work aimed to produce a polyclonal antiserum in mice and test its ability to neutralize the main toxic effects induced by the venoms of the main venomous Brazilian fish. We found that the antiserum recognizes the main toxins present in the different venoms of Thalassophryne nattereri, Scorpaena plumieri, Potamotrygon gr. Orbignyi, and Cathorops spixii and was effective in pre-incubation trials. In an independent test, the antiserum applied immediately to the topical application of T. nattereri, P. gr orbygnyi, and C. spixii venoms completely abolished the toxic effects on the microcirculation, preventing alterations such as arteriolar contraction, slowing of blood flow in postcapillary venules, venular stasis, myofibrillar hypercontraction, and increased leukocyte rolling and adherence. The edematogenic and nociceptive activities induced by these venoms were also neutralized by the immediate application of the antiserum. Importantly, the antiserum prevented the acute inflammatory response in the lungs induced by the S. plumieri venom. The success of antiserum containing neutralizing polyclonal antibodies in controlling the toxic effects induced by different venoms offers a new strategy for the treatment of fish envenomation in Brazil.
Growth State-Dependent Activation of eNOS in Response to DHA: Involvement of p38 MAPK
Authors: Huang Shiqi , Taylor Carla G. , Zahradka Peter
Published: May 2023

Our laboratory previously reported that docosahexaenoic acid (DHA) differentially activates p38 mitogen-activated protein kinase (MAPK) in growing and quiescent human endothelial cells, which represent the dysfunctional and healthy states in vivo, respectively. Since endothelial nitric oxide synthase (eNOS) activity differs between healthy and dysfunctional endothelial cells, and p38 MAPK reportedly regulates both the activity and expression of eNOS, we hypothesized that the beneficial actions of DHA on endothelial cells are due to eNOS activation by p38 MAPK. The contribution of mitogen- and stress-activated protein kinase (MSK), a p38 MAPK substrate, was also investigated. Growing and quiescent EA.hy926 cells, prepared on Matrigel®-coated plates, were incubated with inhibitors of p38MAPK or MSK before adding DHA. eNOS phosphorylation and levels were quantified by Western blotting. Treatment with 20 µM DHA activated eNOS in both growth states whereas 125 µM DHA suppressed eNOS activation in growing cells. Quiescent cells had higher basal levels of eNOS than growing cells, while 125 µM DHA decreased eNOS levels in both growth states. p38 MAPK inhibition enhanced eNOS activation in quiescent cells but suppressed it in growing cells. Interestingly, 125 µM DHA counteracted these effects of p38 MAPK inhibition in both growth states. MSK was required for eNOS activation in both growth states, but it only mediated eNOS activation by DHA in quiescent cells. MSK thus affects eNOS via a pathway independent of p38MAPK. Quiescent cells were also more resistant to the apoptosis-inducing effect of 125 µM DHA compared to growing cells. The growth state-dependent regulation of p38MAPK and eNOS by DHA provides novel insight into the molecular mechanisms by which DHA influences endothelial cell function.
Gene Expression Behavior of a Set of Genes in Platelet and Tissue Samples from Patients with Breast Cancer
Authors: Burciaga-Hernandez Luis A. , Cueto-Villalobos Cecilia F. , Ortega-Piñon Nancy , Gonzalez-Curiel Irma E. , Godina-Gonzalez Susana , Mendez-Frausto Gwendolyne , Aguilar-Esquivel Anna P. , Maldonado-Lagunas Vilma , Guerrero-de la Torre Luis E. , Melendez-Zajgla Jorge , Sanchez-Garcia Erika K. , Mitre-Aguilar Irma B. , Mendoza-Almanza Gretel
Published: May 2023

The tumor microenvironment (TME) is constituted by a great diversity of highly dynamic cell populations, each of which contributes ligands, receptors, soluble proteins, mRNAs, and miRNAs, in order to regulate cellular activities within the TME and even promote processes such as angiogenesis or metastasis. Intravasated platelets (PLT) undergo changes in the TME that convert them into tumor-educated platelets (TEP), which supports the development of cancer, angiogenesis, and metastasis through the degranulation and release of biomolecules. Several authors have reported that the deregulation of PF4, VEGF, PDGF, ANG-1, WASF3, LAPTM4B, TPM3, and TAC1 genes participates in breast cancer progression, angiogenesis, and metastasis. The present work aimed to analyze the expression levels of this set of genes in tumor tissues and platelets derived from breast cancer patients by reverse transcription-quantitative polymerase chain reaction (RTqPCR) assays, in order to determine if there was an expression correlation between these sources and to take advantage of the new information to be used in possible diagnosis by liquid biopsy. Data from these assays showed that platelets and breast cancer tumors present similar expression levels of a subset of these genes’ mRNAs, depending on the molecular subtype, comorbidities, and metastasis presence.
Assembly of the Complete Mitochondrial Genome of Pereskia aculeata Revealed That Two Pairs of Repetitive Elements Mediated the Recombination of the Genome
Authors: Zhang Xue , Shan Yuanyu , Li Jingling , Qin Qiulin , Yu Jie , Deng Hongping
Published: May 2023

Pereskia aculeata is a potential new crop species that has both food and medicinal (antinociceptive activity) properties. However, comprehensive genomic research on P. aculeata is still lacking, particularly concerning its organelle genome. In this study, P. aculeata was studied to sequence the mitochondrial genome (mitogenome) and to ascertain the assembly, informational content, and developmental expression of the mitogenome. The findings revealed that the mitogenome of P. aculeata is circular and measures 515,187 bp in length with a GC content of 44.05%. It contains 52 unique genes, including 33 protein-coding genes, 19 tRNA genes, and three rRNA genes. Additionally, the mitogenome analysis identified 165 SSRs, primarily consisting of tetra-nucleotides, and 421 pairs of dispersed repeats with lengths greater than or equal to 30, which were mainly forward repeats. Based on long reads and PCR experiments, we confirmed that two pairs of long-fragment repetitive elements were highly involved with the mitogenome recombination process. Furthermore, there were 38 homologous fragments detected between the mitogenome and chloroplast genome, and the longest fragment was 3962 bp. This is the first report on the mitogenome in the family Cactaceae. The decoding of the mitogenome of P. aculeata will provide important genetic materials for phylogenetic studies of Cactaceae and promote the utilization of species germplasm resources.
Distinct Profiles of Desensitization of µ-Opioid Receptors Caused by Remifentanil or Fentanyl: In Vitro Assay with Cells and Three-Dimensional Structural Analyses
Authors: Uezono Eiko , Mizobuchi Yusuke , Miyano Kanako , Ohbuchi Katsuya , Murata Hiroaki , Komatsu Akane , Manabe Sei , Nonaka Miki , Hirokawa Takatsugu , Yamaguchi Keisuke , Iseki Masako , Uezono Yasuhito , Hayashida Masakazu , Kawagoe Izumi
Published: May 2023

Remifentanil (REM) and fentanyl (FEN) are commonly used analgesics that act by activating a µ-opioid receptor (MOR). Although optimal concentrations of REM can be easily maintained during surgery, it is sometimes switched to FEN for optimal pain regulation. However, standards for this switching protocol remain unclear. Opioid anesthetic efficacy is decided in part by MOR desensitization; thus, in this study, we investigated the desensitization profiles of REM and FEN to MOR. The efficacy and potency during the 1st administration of REM or FEN in activating the MOR were almost equal. Similarly, in β arrestin recruitment, which determines desensitization processes, they showed no significant differences. In contrast, the 2nd administration of FEN resulted in a stronger MOR desensitization potency than that of REM, whereas REM showed a higher internalization potency than FEN. These results suggest that different β arrestin-mediated signaling caused by FEN or REM led to their distinct desensitization and internalization processes. Our three-dimensional analysis, with in silico binding of REM and FEN to MOR models, highlighted that REM and FEN bound to similar but distinct sites of MOR and led to distinct β arrestin-mediated profiles, suggesting that distinct binding profiles to MOR may alter β arrestin activity, which accounts for MOR desensitization and internalization.
Enhancement of Sphingomyelinase-Induced Endothelial Nitric Oxide Synthase-Mediated Vasorelaxation in a Murine Model of Type 2 Diabetes
Authors: Ruisanchez Éva , Janovicz Anna , Panta Rita Cecília , Kiss Levente , Párkányi Adrienn , Straky Zsuzsa , Korda Dávid , Liliom Károly , Tigyi Gábor , Benyó Zoltán
Published: May 2023

Sphingolipids are important biological mediators both in health and disease. We investigated the vascular effects of enhanced sphingomyelinase (SMase) activity in a mouse model of type 2 diabetes mellitus (T2DM) to gain an understanding of the signaling pathways involved. Myography was used to measure changes in the tone of the thoracic aorta after administration of 0.2 U/mL neutral SMase in the presence or absence of the thromboxane prostanoid (TP) receptor antagonist SQ 29,548 and the nitric oxide synthase (NOS) inhibitor L-NAME. In precontracted aortic segments of non-diabetic mice, SMase induced transient contraction and subsequent weak relaxation, whereas vessels of diabetic (Leprdb/Leprdb, referred to as db/db) mice showed marked relaxation. In the presence of the TP receptor antagonist, SMase induced enhanced relaxation in both groups, which was 3-fold stronger in the vessels of db/db mice as compared to controls and could not be abolished by ceramidase or sphingosine-kinase inhibitors. Co-administration of the NOS inhibitor L-NAME abolished vasorelaxation in both groups. Our results indicate dual vasoactive effects of SMase: TP-mediated vasoconstriction and NO-mediated vasorelaxation. Surprisingly, in spite of the general endothelial dysfunction in T2DM, the endothelial NOS-mediated vasorelaxant effect of SMase was markedly enhanced.
In Silico Design of New Dual Inhibitors of SARS-CoV-2 MPRO through Ligand- and Structure-Based Methods
Authors: Bono Alessia , Lauria Antonino , La Monica Gabriele , Alamia Federica , Mingoia Francesco , Martorana Annamaria
Published: May 2023

The viral main protease is one of the most attractive targets among all key enzymes involved in the life cycle of SARS-CoV-2. Considering its mechanism of action, both the catalytic and dimerization regions could represent crucial sites for modulating its activity. Dual-binding the SARS-CoV-2 main protease inhibitors could arrest the replication process of the virus by simultaneously preventing dimerization and proteolytic activity. To this aim, in the present work, we identified two series’ of small molecules with a significant affinity for SARS-CoV-2 MPRO, by a hybrid virtual screening protocol, combining ligand- and structure-based approaches with multivariate statistical analysis. The Biotarget Predictor Tool was used to filter a large in-house structural database and select a set of benzo[b]thiophene and benzo[b]furan derivatives. ADME properties were investigated, and induced fit docking studies were performed to confirm the DRUDIT prediction. Principal component analysis and docking protocol at the SARS-CoV-2 MPRO dimerization site enable the identification of compounds 1b,c,i,l and 2i,l as promising drug molecules, showing favorable dual binding site affinity on SARS-CoV-2 MPRO.
Multicomponent Antibiofilm Lipid Nanoparticles as Novel Platform to Ameliorate Resveratrol Properties: Preliminary Outcomes on Fibroblast Proliferation and Migration
Authors: Angellotti Giuseppe , Di Prima Giulia , D'Agostino Fabio , Peri Emanuela , Tricoli Maria Rita , Belfiore Elena , Allegra Mario , Cancemi Patrizia , De Caro Viviana
Published: May 2023

The well-being of skin and mucous membranes is fundamental for the homeostasis of the body and thus it is imperative to treat any lesion quickly and correctly. In this view, polyphenols might assist and enhance a successful wound healing process by reducing the inflammatory cascade and the production of free radicals. However, they suffer from disadvantageous physico–chemical properties, leading to restricted clinical use. In this work, a complex mixture of PEGylated lipid, Glyceryl monoester, 18-β-Glycyrrhetinic Acid and Menthol was designed to entrap Resveratrol (RSV) as the active ingredient and further produce lipid nanoparticles (LNPs) by homogenization followed by high-frequency sonication. The nanosystem was properly characterized in terms of particle size (DLS, SEM), zeta potential, drug loading, antioxidant power (DPPH), release behaviour, cytocompatibility, wound healing and antibiofilm properties. The optimized lipid mixture was homogeneous, melted at 57–61 °C and encapsulated amorphous RSV (4.56 ± 0.04% w/w). The RSV-loaded LNPs were almost monodispersed (PDI: 0.267 ± 0.010), with nanometric size (162.86 ± 3.12 nm), scavenger properties and suitable DR% and LE% values (96.82 ± 1.34% and 95.17 ± 0.25%, respectively). The release studies were performed to simulate the wound conditions: 1-octanol to mimic the lipophilic domains of biological tissues (where the First Order kinetic was observed) and citrate buffer pH 5.5 according to the inflammatory wound exudate (where the Korsmeyer–Peppas kinetic was followed). The biological and microbiological evaluations highlighted fibroblast proliferation and migration effects as well as antibiofilm properties at extremely low doses (LNPs: 22 μg/mL, corresponding to RSV 5 µM). Thus, the proposed multicomponent LNPs could represent a valuable RSV delivery platform for wound healing purposes.
Identification of Photosynthesis Characteristics and Chlorophyll Metabolism in Leaves of Citrus Cultivar (Harumi) with Varying Degrees of Chlorosis
Authors: Xiong Bo , Li Ling , Li Qin , Mao Huiqiong , Wang Lixinyi , Bie Yuhui , Zeng Xin , Liao Ling , Wang Xun , Deng Honghong , Zhang Mingfei , Sun Guochao , Wang Zhihui
Published: May 2023

In autumn and spring, citrus leaves with a Ponkan (Citrus reticulata Blanco cv. Ponkan) genetic background (Harumi, Daya, etc.) are prone to abnormal physiological chlorosis. The effects of different degrees of chlorosis (normal, mild, moderate and severe) on photosynthesis and the chlorophyll metabolism of leaves of Citrus cultivar (Harumi) were studied via field experiment. Compared with severe chlorotic leaves, the results showed that chlorosis could break leaf metabolism balance, including reduced chlorophyll content, photosynthetic parameters, antioxidant enzyme activity and enzyme activity related to chlorophyll synthesis, increased catalase and decreased enzyme activity. In addition, the content of chlorophyll synthesis precursors showed an overall downward trend expected for uroporphyrinogen III. Furthermore, the relative expression of genes for chlorophyll synthesis (HEMA1, HEME2, HEMG1 and CHLH) was down-regulated to some extent and chlorophyll degradation (CAO, CLH, PPH, PAO and SGR) showed the opposite trend with increased chlorosis. Changes in degradation were more significant. In general, the chlorosis of Harumi leaves might be related to the blocked transformation of uroporphyrinogen III (Urogen III) to coproporphyrinogen III (Coprogen III), the weakening of antioxidant enzyme system activity, the weakening of chlorophyll synthesis and the enhancement in degradation.
A Predictive Model of Adaptive Resistance to BRAF/MEK Inhibitors in Melanoma
Authors: Ruiz Emmanuelle M. , Alhassan Solomon A. , Errami Youssef , Abd Elmageed Zakaria Y. , Fang Jennifer S. , Wang Guangdi , Brooks Margaret A. , Abi-Rached Joe A. , Kandil Emad , Zerfaoui Mourad
Published: May 2023

The adaptive acquisition of resistance to BRAF and MEK inhibitor-based therapy is a common feature of melanoma cells and contributes to poor patient treatment outcomes. Leveraging insights from a proteomic study and publicly available transcriptomic data, we evaluated the predictive capacity of a gene panel corresponding to proteins differentially abundant between treatment-sensitive and treatment-resistant cell lines, deciphering predictors of treatment resistance and potential resistance mechanisms to BRAF/MEK inhibitor therapy in patient biopsy samples. From our analysis, a 13-gene signature panel, in both test and validation datasets, could identify treatment-resistant or progressed melanoma cases with an accuracy and sensitivity of over 70%. The dysregulation of HMOX1, ICAM, MMP2, and SPARC defined a BRAF/MEK treatment-resistant landscape, with resistant cases showing a >2-fold risk of expression of these genes. Furthermore, we utilized a combination of functional enrichment- and gene expression-derived scores to model and identify pathways, such as HMOX1-mediated mitochondrial stress response, as potential key drivers of the emergence of a BRAF/MEK inhibitor-resistant state in melanoma cells. Overall, our results highlight the utility of these genes in predicting treatment outcomes and the underlying mechanisms that can be targeted to reduce the development of resistance to BRAF/MEK targeted therapy.
Current Levels of Environmental Exposure to Cadmium in Industrialized Countries as a Risk Factor for Kidney Damage in the General Population: A Comprehensive Review of Available Data
Authors: Smereczański Nazar M. , Brzóska Małgorzata M.
Published: May 2023

The growing number of reports indicating unfavorable outcomes for human health upon environmental exposure to cadmium (Cd) have focused attention on the threat to the general population posed by this heavy metal. The kidney is a target organ during chronic Cd intoxication. The aim of this article was to critically review the available literature on the impact of the current levels of environmental exposure to this xenobiotic in industrialized countries on the kidney, and to evaluate the associated risk of organ damage, including chronic kidney disease (CKD). Based on a comprehensive review of the available data, we recognized that the observed adverse effect levels (NOAELs) of Cd concentration in the blood and urine for clinically relevant kidney damage (glomerular dysfunction) are 0.18 μg/L and 0.27 μg/g creatinine, respectively, whereas the lowest observed adverse effect levels (LOAELs) are >0.18 μg/L and >0.27 μg/g creatinine, respectively, which are within the lower range of concentrations noted in inhabitants of industrialized countries. In conclusion, the current levels of environmental exposure to Cd may increase the risk of clinically relevant kidney damage, resulting in, or at least contributing to, the development of CKD.
Assessing the Relationship between Systemic Immune-Inflammation Index and Metabolic Syndrome in Children with Obesity
Authors: Nicoară Delia-Maria , Munteanu Andrei-Ioan , Scutca Alexandra-Cristina , Mang Niculina , Juganaru Iulius , Brad Giorgiana-Flavia , Mărginean Otilia
Published: May 2023

Childhood obesity represents a worldwide concern as many countries have reported an increase in its incidence, with possible cardiovascular long-term implications. The mechanism that links cardiovascular disease to obesity is related to low-grade inflammation. We designed this study to investigate the diagnostic utility of inflammatory indices (NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; SII, systemic immune-inflammation index; SIRI, systemic inflammation response index) in obese children with metabolic syndrome (MetS) and their relationship with cardiometabolic risk biomarkers, such as the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), triglyceride-to-high-density lipoprotein cholesterol (TG:HDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). A total of 191 obese children from one large Romanian reference center was included in the study. Patients were classified in two groups according to the presence (MetS group) or absence (non-MetS group) of metabolic syndrome. According to our results, the SII index proved to have diagnostic value in distinguishing MetS patients among children with obesity (AUC = 0.843, a sensitivity of 0.83, and a specificity of 0.63). Furthermore, the SII was positively associated with cardiometabolic risk biomarkers (HOMA-IR, p < 0.001; TG:HDL-C, p = 0.002; non-HDL-C, p = 0.021), highlighting its possible role as an additional measure of cardiometabolic instability in obese children.
Genome-Wide Association Study Identifies Genetic Polymorphisms Associated with Estimated Minimum Effective Concentration of Fentanyl in Patients Undergoing Laparoscopic-Assisted Colectomy
Authors: Nishizawa Daisuke , Mieda Tsutomu , Tsujita Miki , Nakagawa Hideyuki , Yamaguchi Shigeki , Kasai Shinya , Hasegawa Junko , Nakayama Kyoko , Ebata Yuko , Kitamura Akira , Shimizu Hirotomo , Takashima Tadayuki , Hayashida Masakazu , Ikeda Kazutaka
Published: May 2023

Sensitivity to opioids varies widely among individuals. To identify potential candidate single-nucleotide polymorphisms (SNPs) that may significantly contribute to individual differences in the minimum effective concentration (MEC) of an opioid, fentanyl, we conducted a three-stage genome-wide association study (GWAS) using whole-genome genotyping arrays in 350 patients who underwent laparoscopic-assisted colectomy. To estimate the MEC of fentanyl, plasma and effect-site concentrations of fentanyl over the 24 h postoperative period were estimated with a pharmacokinetic simulation model based on initial bolus doses and subsequent patient-controlled analgesia doses of fentanyl. Plasma and effect-site MECs of fentanyl were indicated by fentanyl concentrations, estimated immediately before each patient-controlled analgesia dose. The GWAS revealed that an intergenic SNP, rs966775, that mapped to 5p13 had significant associations with the plasma MEC averaged over the 6 h postoperative period and the effect-site MEC averaged over the 12 h postoperative period. The minor G allele of rs966775 was associated with increases in these MECs of fentanyl. The nearest protein-coding gene around this SNP was DRD1, encoding the dopamine D1 receptor. In the gene-based analysis, the association was significant for the SERP2 gene in the dominant model. Our findings provide valuable information for personalized pain treatment after laparoscopic-assisted colectomy.
Artificial Intelligence Technologies in Cardiology
Authors: Ledziński Łukasz , Grześk Grzegorz
Published: May 2023

As the world produces exabytes of data, there is a growing need to find new methods that are more suitable for dealing with complex datasets. Artificial intelligence (AI) has significant potential to impact the healthcare industry, which is already on the road to change with the digital transformation of vast quantities of information. The implementation of AI has already achieved success in the domains of molecular chemistry and drug discoveries. The reduction in costs and in the time needed for experiments to predict the pharmacological activities of new molecules is a milestone in science. These successful applications of AI algorithms provide hope for a revolution in healthcare systems. A significant part of artificial intelligence is machine learning (ML), of which there are three main types—supervised learning, unsupervised learning, and reinforcement learning. In this review, the full scope of the AI workflow is presented, with explanations of the most-often-used ML algorithms and descriptions of performance metrics for both regression and classification. A brief introduction to explainable artificial intelligence (XAI) is provided, with examples of technologies that have developed for XAI. We review important AI implementations in cardiology for supervised, unsupervised, and reinforcement learning and natural language processing, emphasizing the used algorithm. Finally, we discuss the need to establish legal, ethical, and methodical requirements for the deployment of AI models in medicine.
Effect of Nanostructured Silica Additives on the Extrusion-Based 3D Concrete Printing Application
Authors: Liu Zhenbang , Li Mingyang , Moo Guo Sheng James , Kobayashi Hitoshi , Wong Teck Neng , Tan Ming Jen
Published: May 2023

Recently, 3D printing technology has become more popular in the field of construction. For the extrusion-based 3D concrete printing (3DCP) process, the cementitious material needs to be strong and flowable enough to ensure buildability and pumpability. Nanostructured silica, a kind of additive, has been used to modify the 3DCP concrete to meet these requests. However, most previous studies focused on the effect of nanostructured silica on rheological properties and failed to link the obtained rheological properties of nanostructured-silica-modified cementitious materials to the performance in 3D printing. In this paper, the 3DCP mixture based on premix cement, river sand, silica fume, and water was modified by different dosages of nanostructured silica (from 0.25% to 1.00% by the total weight of the 3DCP mixture). The effects of nanostructured silica on the rheological, hydration, printing, and microstructural properties were determined by rheological tests, stress growth tests, setting time tests, printing tests, and scanning electron microscopy (SEM) tests, respectively. This paper revealed that the nanostructured silica has a positive effect on 3DCP buildability but negatively affects the printing quality, which fits the effect of nanostructured silica on the rheological properties. Hence, the determined rheological properties can qualitatively evaluate the printing performance of nanostructured-silica-modified cementitious materials.
Vocal Cord Paralysis and Feeding Difficulties as Early Diagnostic Clues of Congenital Myasthenic Syndrome with Neonatal Onset: A Case Report and Review of Literature
Authors: De Rose Domenico Umberto , Ronci Sara , Caoci Stefano , Maddaloni Chiara , Diodato Daria , Catteruccia Michela , Fattori Fabiana , Bosco Luca , Pro Stefano , Savarese Immacolata , Bersani Iliana , Randi Franco , Trozzi Marilena , Meucci Duino , Calzolari Flaminia , Salvatori Guglielmo , Solinas Agostina , Dotta Andrea , Campi Francesca
Published: May 2023

Herein, we present a newborn female with congenital vocal cord paralysis who required a tracheostomy in the neonatal period. She also presented with feeding difficulties. She was later diagnosed with a clinical picture of congenital myasthenia, associated with three variants of the MUSK gene: the 27-month follow-up was described. In particular, the c.565C>T variant is novel and has never been described in the literature; it causes the insertion of a premature stop codon (p.Arg189Ter) likely leading to a consequent formation of a truncated nonfunctioning protein. We also systematically collected and summarized information on patients’ characteristics of previous cases of congenital myasthenia with neonatal onset reported in the literature to date, and we compared them to our case. The literature reported 155 neonatal cases before our case, from 1980 to March 2022. Of 156 neonates with CMS, nine (5.8%) had vocal cord paralysis, whereas 111 (71.2%) had feeding difficulties. Ocular features were evident in 99 infants (63.5%), whereas facial-bulbar symptoms were found in 115 infants (73.7%). In one hundred sixteen infants (74.4%), limbs were involved. Respiratory problems were displayed by 97 infants (62.2%). The combination of congenital stridor, particularly in the presence of an apparently idiopathic bilateral vocal cord paralysis, and poor coordination between sucking and swallowing may indicate an underlying congenital myasthenic syndrome (CMS). Therefore, we suggest testing infants with vocal cord paralysis and feeding difficulties for MUSK and related genes to avoid a late diagnosis of CMS and improve outcomes.
English and Co-Construction of Solidarity between Language Agents and Tourists in Tourism Information Service
Authors: Yusra Kamaludin
Published: May 2023

A substantial number of studies have been completed with respect to the use of English and social solidarity in broader contexts of cross-cultural communications including tourist–host interactions in tourism settings, but little, if any, is understood about the use of English and solidarity in hectic and tightly scheduled international airport settings. This study fills the gap by explicating how English is used by Tourist Information Center (TIC) staffs and incoming tourists at Lombok International Airport (LIA), Lombok, Indonesia, to contextually symbolize solidarity among them. Data were collected in more than a year of intensive participant and non-participant ethnographic observations of real-time interactions at the TIC in the LIA. Recordings, introspective, retrospective, and prospective interviews with the staff and the tourist respondents, as well as note takings of the contexts and the situations of communicative events, were the main means of data collection, and these data were analyzed using integration of sociological analyses of solidarity and ethnographic analyses of communicative interactions. The study elucidates ideological views on the service and explicates how speech accommodation, style convergence, code switching, and kinship terms have been employed as strategies for creating symbolic solidarity.
New 5-Chloro-Maleonitrile-Salen Ligand and Relative Co(II) Complex
Authors: Cavallaro Alessia , Santonocito Rossella , Puglisi Roberta , Pappalardo Andrea , Trusso Sfrazzetto Giuseppe
Published: May 2023

Salen ligands and relative metal complexes are widely used in many fields, such as catalysis, sensing, optical and electronic materials. The introduction of a wide range of substituents in different positions, both in the salen scaffold and in the diamine bridge, allows the tuning of chemical, catalytic and spectroscopic properties. In this contribution, we report the synthesis and characterization of a new salen ligand and relative Co(II) complex bearing a maleonitrile bridge and two chlorine atoms in the salen backbone.
5-(1-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-phenylethyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione
Authors: Ryzhkova Yuliya E. , Kalashnikova Varvara M. , Ryzhkov Fedor V. , Elinson Michail N.
Published: May 2023

Multicomponent reactions have been demonstrated as a promising tool for the creation of diverse molecular structures with enhanced efficiency, reduced waste, and a high atom economy. Arylglyoxal monohydrates with two different carbonyl groups are well known as worthwhile synthons in organic synthesis. 2-Pyrone and pyrimidine-2,4,6-trione are versatile building blocks for the synthesis of key intermediates in synthetic organic chemistry as well as in medicinal chemistry. A simple and efficient tandem Knoevenagel–Michael protocol for the synthesis of the previously unknown 5-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-phenylethyl)-1,3-dimet-hylpyrimidine-2,4,6(1H,3H,5H)-trione was elaborated. The suggested method is based on the multicomponent reaction of phenylglyoxal hydrate, 1,3-dimethylbarbituric acid, and 4-hydroxy-6-methyl-2H-pyran-2-one. The structure of the synthesized compound was proven by 1H, 13C-NMR, and IR spectroscopy, mass spectrometry, and elemental analysis. A procedure for predicting the possible types of its biological activity was carried out for the title compound.
Insights into the Microscopic Oil–Water Flow Characteristics and Displacement Mechanisms during Waterflooding in Sandstone Reservoir Rock Based on Micro-CT Technology: A Pore-Scale Numerical Simulation Study
Authors: Hu Bingtao , Chai Guoliang , Liu Xingjun , Wen Xiaofeng , Gu Zhaolin , Xie Liaobo , Han Shifeng , Su Junwei
Published: May 2023

The low oil recovery rate observed in current oil fields is largely attributed to the presence of remaining oil trapped in the pores of porous media during waterflooding. To improve the recovery rate, it is imperative to gain an understanding of the oil–water flow characteristics and displacement mechanisms during waterflooding, as well as to elucidate the underlying mobilization mechanisms of residual oil at the pore scale. In this paper, we explore these issues in depth by numerically investigating the influence of factors such as water injection velocities, oil–water viscosity ratios, and wettability conditions on pore-scale oil–water flow characteristics and oil recovery rate. To this end, we employ a direct numerical simulation (DNS) method in conjunction with the volume of fluid (VOF) method to study the microscopic displacement mechanisms of waterflooding in a reconstructed two-dimensional digital rock core based on micro-CT technology. In addition, the particle tracing method is adopted to identify the flow path and dominant areas during waterflooding in order to mobilize the residual oil within the pores. The findings indicate that the oil–water flow characteristics in porous media are determined by the interplay between capillary and viscous forces. Furthermore, the oil recovery rate is 10.6% and 24.7% lower under strong water-wet and oil-wet conditions than that (32.36%) under intermediate wettability conditions, and the final oil recovery rate is higher under water-wet conditions than under oil-wet conditions. The seepage path and the dominant areas are directly linked to the capillarity formed during waterflooding. The findings of this study are significant in terms of enhancing the recovery rate of residual oil and provide a novel perspective for understanding the waterflooding process.
Review: Inelastic Constitutive Modeling: Polycrystalline Materials
Authors: Baig Mirza , Owusu-Danquah Josiah , Campbell Anne A. , Duffy Stephen F.
Published: May 2023

This article provides a literature review that details the development of inelastic constitutive modeling as it relates to polycrystalline materials. This review distinguishes between inelastic constitutive models that account for nonlinear behavior at the microstructural level, time-independent classic plasticity models, and time-dependent unified models. Particular emphasis is placed on understanding the underlying theoretical framework for unified viscoplasticity models where creep and classical plasticity behavior are considered the result of applied boundary conditions instead of separable rates representing distinct physical mechanisms. This article establishes a clear understanding of the advantages of the unified approach to improve material modeling. This review also discusses recent topics in constitutive modeling that offer new techniques that bridge the gap between the microstructure and the continuum.
Recent Progress for Single-Molecule Magnets Based on Rare Earth Elements
Authors: Yin Xiang , Deng Li , Ruan Liuxia , Wu Yanzhao , Luo Feifei , Qin Gaowu , Han Xiaoli , Zhang Xianmin
Published: May 2023

Single-molecule magnets (SMMs) have attracted much attention due to their potential applications in molecular spintronic devices. Rare earth SMMs are considered to be the most promising for application owing to their large magnetic moment and strong magnetic anisotropy. In this review, the recent progress in rare earth SMMs represented by mononuclear and dinuclear complexes is highlighted, especially for the modulation of magnetic anisotropy, effective energy barrier (Ueff) and blocking temperature (TB). The terbium- and dysprosium-based SMMs have a Ueff of 1541 cm−1 and an increased TB of 80 K. They break the boiling point temperature of liquid nitrogen. The development of the preparation technology of rare earth element SMMs is also summarized in an overview. This review has important implications and insights for the design and research of Ln-SMMs.
Microstructure Evolution and Mechanical Response of a Direct Quenched and Partitioned Steel at Different Finishing Rolling Temperatures
Authors: Liu Yajun , Gan Xiaolong , Liang Wen , Xu Guang , Qi Jianghua , Liu Man
Published: May 2023

The effects of finishing rolling temperature on the microstructure and mechanical properties of a direct quenched and partitioned (DQ&P) steel were investigated by a thermal simulation machine, a field emission scanning electron microscope (FE-SEM), electron backscattering diffraction (EBSD), and a transmission electron microscope (TEM). The results show that the original austenite grain size was refined by 31% as the finishing rolling temperature decreased from 920 °C to 840 °C, leading to the formation of the finest martensite lath at 840 °C. At the same time, the lower finishing rolling temperature resulted in a higher dislocation density, and consequently improved the stability of the retained austenite. Moreover, compared to the conventional Q&P process, the comprehensive mechanical properties of a steel with similar chemical composition can be enhanced by DQ&P processing. With the decrease of finishing rolling temperature from 920 °C to 840 °C, the strength and total elongation increases. The yield strength, tensile strength, and total elongation reach the maximum values of 1121 MPa, 1134 MPa, and 11.7%, respectively, at 840 °C.