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Article
Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches
Molecules 2022, 27(12), 3888; https://doi.org/10.3390/molecules27123888 (registering DOI) - 17 Jun 2022
Abstract
Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential [...] Read more.
Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery. Full article
(This article belongs to the Special Issue Coumarin and Its Derivatives II)
Article
Over-Expression of Larch DAL1 Accelerates Life-Cycle Progression in Arabidopsis
Forests 2022, 13(6), 953; https://doi.org/10.3390/f13060953 (registering DOI) - 17 Jun 2022
Abstract
Homologs of Larix kaempferiDEFICIENS-AGAMOUS-LIKE 1 (LaDAL1) promote flowering in Arabidopsis. However, their functional role in the whole life-cycle is limited. Here, we analyzed the phenotypes and transcriptomes of Arabidopsis plants over-expressing LaDAL1. With respect to the defined life-cycle [...] Read more.
Homologs of Larix kaempferiDEFICIENS-AGAMOUS-LIKE 1 (LaDAL1) promote flowering in Arabidopsis. However, their functional role in the whole life-cycle is limited. Here, we analyzed the phenotypes and transcriptomes of Arabidopsis plants over-expressing LaDAL1. With respect to the defined life-cycle stage of Arabidopsis based on the meristem state, the results showed that LaDAL1 promoted seed germination, bolting, flower initiation, and global proliferative arrest, indicating that LaDAL1 accelerates the meristem reactivation, the transitions of vegetative meristem to inflorescence and flower meristem, and meristem arrest. As a marker gene of meristem, TERMINAL FLOWER 1 was down-regulated after LaDAL1 over-expression. These results reveal that LaDAL1 accelerates the life-cycle progression in Arabidopsis by promoting the transition of meristem fate, providing more and novel functional information about the conifer age-related gene DAL1. Full article
(This article belongs to the Special Issue Tree Genetics: Molecular and Functional Characterization of Genes)
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Article
Structure, Spectra and Photochemistry of 2-Amino-4-Methylthiazole: FTIR Matrix Isolation and Theoretical Studies
Molecules 2022, 27(12), 3897; https://doi.org/10.3390/molecules27123897 (registering DOI) - 17 Jun 2022
Abstract
The structure, tautomerization pathways, vibrational spectra, and photochemistry of 2-amino-4-methylthiazole (AMT) molecule were studied by matrix isolation FTIR spectroscopy and DFT calculations undertaken at the B3LYP/6-311++G(3df,3pd) level of theory. The most stable tautomer with the five-membered ring stabilized by two double C=C and [...] Read more.
The structure, tautomerization pathways, vibrational spectra, and photochemistry of 2-amino-4-methylthiazole (AMT) molecule were studied by matrix isolation FTIR spectroscopy and DFT calculations undertaken at the B3LYP/6-311++G(3df,3pd) level of theory. The most stable tautomer with the five-membered ring stabilized by two double C=C and C=N bonds, was detected in argon matrices after deposition. When the AMT/Ar matrices were exposed to 265 nm selective irradiation, three main photoproducts, N-(1-sulfanylprop-1-en-2-yl)carbodiimide (fp1), N-(1-thioxopropan-2-yl)carbodiimide (fp2) and N-(2-methylthiiran-2-yl)carbodiimide (fp3), were photoproduced by a cleavage of the CS–CN bond together with hydrogen atom migration. The minor photoreaction caused by the cleavage of the CS–CC bond and followed by hydrogen migration formed 2-methyl-1H-azirene-1-carbimidothioic acid (fp15). We have also found that cleavage of the CS–CN bond followed by disruption of the N–C bond produced cyanamide (fp11) and the ˙C(CH3)=CH–S˙ biradical that transformed into 2-methylthiirene (fp12) and further photoreactions produced 1-propyne-1-thiole (fp13) or methylthioketene (fp14). Cleavage of the CS–CC bond followed by disruption of the N–C bond produced propyne (fp22) and the ˙S–C(NH2)=N˙ biradical that transformed into 3-aminethiazirene (fp23); further photoreactions produced N-sulfanylcarbodiimide (fp25). As a result of these transformations, several molecular complexes were identified as photoproducts besides new molecules in the AMT photolysis process. Full article
(This article belongs to the Special Issue Advances in Computational Spectroscopy)
Article
Metabolome Alterations Linking Sugar-Sweetened Beverage Intake with Dyslipidemia in Youth: The Exploring Perinatal Outcomes among CHildren (EPOCH) Study
Metabolites 2022, 12(6), 559; https://doi.org/10.3390/metabo12060559 (registering DOI) - 17 Jun 2022
Abstract
The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in [...] Read more.
The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in childhood (median 10 yrs) and adolescence (median 16 yrs). We used a multi-step approach: first, mixed models were used to examine the associations of SSB intake in childhood with CM measures across childhood and adolescence, which revealed a positive association between SSB intake and fasting triglycerides (β (95% CI) for the highest vs. lowest SSB quartile: 8.1 (−0.9,17.0); p-trend = 0.057). Second, least absolute shrinkage and selection operator (LASSO) regression was used to select 180 metabolite features (out of 767 features assessed by untargeted metabolomics) that were associated with SSB intake in childhood. Finally, 13 of these SSB-associated metabolites (from step two) were also prospectively associated with triglycerides across follow-up (from step one) in the same direction as with SSB intake (Bonferroni-adj. p < 0.0003). All annotated compounds were lipids, particularly dicarboxylated fatty acids, mono- and diacylglycerols, and phospholipids. In this diverse cohort, we identified a panel of lipid metabolites that may serve as intermediary biomarkers, linking SSB intake to dyslipidemia risk in youth. Full article
(This article belongs to the Special Issue Determinants, Mechanisms, and Consequences of Childhood Obesity)
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Article
Racemic Norlignans as Diastereoisomers from Ferula sinkiangensis Resins with Antitumor and Wound-Healing Promotion Activities
Molecules 2022, 27(12), 3907; https://doi.org/10.3390/molecules27123907 (registering DOI) - 17 Jun 2022
Abstract
Ferulasinkins A–D (14), four new norlignans, were isolated from the resins of Ferula sinkiangensis, a medicinal plant of the Apiaceae family. All of them were obtained as racemic mixtures, chiral HPLC was used to produce their (+)- and [...] Read more.
Ferulasinkins A–D (14), four new norlignans, were isolated from the resins of Ferula sinkiangensis, a medicinal plant of the Apiaceae family. All of them were obtained as racemic mixtures, chiral HPLC was used to produce their (+)- and (−)-antipodes. The structures of these new compounds, including their absolute configurations, were elucidated by spectroscopic and computational methods. This isolation provides new insight into the chemical profiling of F. sinkiangensis resins beyond the well-investigated structure types such as sesquiterpene coumarins and disulfides. Compounds 2a and 3a were found to significantly inhibit the invasion and migration of triple-negative breast cancer (TNBC) cell lines via CCK-8 assay. On the other hand, the wound-healing assay also demonstrated that compounds 4a and 4b could promote the proliferation of human umbilical vein endothelial cells (HUVECs). Notably, the promoting effects of 4a and 4b were observed as more significant versus a positive control using basic fibroblast growth factor (bFGF). Full article
(This article belongs to the Section Natural Products Chemistry)
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Article
Discovery of Novel Quinazoline Derivatives as Potent Antitumor Agents
Molecules 2022, 27(12), 3906; https://doi.org/10.3390/molecules27123906 (registering DOI) - 17 Jun 2022
Abstract
In this work, we designed and synthesized a novel series of quinazoline derivatives 6-19 and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, [...] Read more.
In this work, we designed and synthesized a novel series of quinazoline derivatives 6-19 and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, compound 18 exhibited nanomolar level inhibitory activity against MGC-803 cells with an IC50 value of 0.85 μM, indicating approximately a 32-fold selectivity against GES-1 (IC50 = 26.75 μM). Further preclinical evaluation showed that compound 18 remarkably inhibited the migration of MGC-803 cells, induced cell cycle arrest at G2/M, and induced MGC-803 apoptosis, resulting in decreasing the expression of both Bcl-2 and Mcl-1, and up-regulating the expression of both Bax and cleaved PARP. No death or obvious pathological damage was observed in mice by acute toxicity assay. The in vivo antitumor evaluation suggested that compound 18 significantly decreased the average tumor volume and tumor weight without any effect on body weight, which is better than 5-Fu. Therefore, compound 18 can be used as a lead compound for the further development of antitumor drugs in the future. Full article
(This article belongs to the Special Issue Novel Anti-cancer Lead Compounds)
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Communication
Characterization of Volatile Flavor Compounds in Supercritical Fluid Separated and Identified in Gurum (Citrulluslanatus Var. colocynthoide) Seed Oil Using HSME and GC–MS
Molecules 2022, 27(12), 3905; https://doi.org/10.3390/molecules27123905 (registering DOI) - 17 Jun 2022
Abstract
In this study, the volatile compound profiles of gurum seed oil were determined using two methods: supercritical CO2 extraction (SFE) and the screw press process (SPP). For volatile compounds extraction and identification, headspace solid-phase micro-extraction (HS-SPME) and GC–MS were used, respectively. A [...] Read more.
In this study, the volatile compound profiles of gurum seed oil were determined using two methods: supercritical CO2 extraction (SFE) and the screw press process (SPP). For volatile compounds extraction and identification, headspace solid-phase micro-extraction (HS-SPME) and GC–MS were used, respectively. A total number of 56 volatile compounds were revealed and identified in oil extracted by SFE, while only 40 compounds were detected in extracted oil by SPP. Acids, aldehydes, esters, ketones, furans, and other components were present in the highest ratio in oil extracted by SFE. In contrast, alcohols and alkenes were found in the highest proportion in oil extracted by SPP. In this study, it was observed that SFE showed an increase in the amounts of volatile compounds and favorably impacted the aroma of gurum seed oil. The results reveal that different extraction methods significantly impact the volatile components of gurum seed oil, and this study can help evaluate the quality of the oil extracted from gurum seeds. Full article
Article
An Inverse Identification Procedure for the Evaluation of Equivalent Loading Conditions for Simplified Numerical Models in Abaqus
Appl. Mech. 2022, 3(2), 663-682; https://doi.org/10.3390/applmech3020039 (registering DOI) - 17 Jun 2022
Abstract
In the finite element simulation process, it is very common to use simplified models to replace the original complex models to reduce the computational cost. To improve the accuracy of simulation with simplified numerical models in Abaqus Explicit, we propose an inverse identification [...] Read more.
In the finite element simulation process, it is very common to use simplified models to replace the original complex models to reduce the computational cost. To improve the accuracy of simulation with simplified numerical models in Abaqus Explicit, we propose an inverse identification procedure to evaluate the equivalent loading conditions to be applied to these simplified models. We construct an objective function to test the correlation between the final deformed shape obtained by simulation on the full models and the simplified models. A Python identification program using the Levenberg–Marquardt algorithm is implemented to optimize this objective function. In parallel to this approach, we propose a data processing step, validated by a dynamic tensile test, to obtain more accurate numerical responses, including data extraction and estimation. Full numerical models for the Taylor test, dynamic tensile test, and dynamic shear test were constructed using Abaqus Explicit FEM code. The complete models were then replaced by simplified models, in which some non-essential parts were removed and some boundary conditions were modified. In order to obtain the same results in terms of the final geometry, the proposed inverse identification procedure is then used to calculate the equivalent impact velocities for the simplified models. Full article
(This article belongs to the Special Issue Impact Mechanics of Materials and Structures)
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Article
Quantum Brain Dynamics and Holography
Dynamics 2022, 2(2), 187-218; https://doi.org/10.3390/dynamics2020010 (registering DOI) - 17 Jun 2022
Abstract
We describe non-equilibrium quantum brain dynamics (QBD) for the breakdown of symmetry and propose the possibility of hologram memory based on QBD. We begin with the Lagrangian density of QBD with water rotational dipole fields and photon fields in 3+1 dimensions, [...] Read more.
We describe non-equilibrium quantum brain dynamics (QBD) for the breakdown of symmetry and propose the possibility of hologram memory based on QBD. We begin with the Lagrangian density of QBD with water rotational dipole fields and photon fields in 3+1 dimensions, and derive time evolution equations of coherent fields. We show a solution for super-radiance derived from the Lagrangian of QBD and propose a scenario of holography by the interference of two incident super-radiant waves. We investigate the time evolution of coherent dipole fields and photon fields in the presence of quantum fluctuations in numerical simulations. We find that the breakdown of the rotational symmetry of dipoles occurs in inverted populations for incoherent dipoles. We show how the waveforms of holograms with interference patterns evolve over time in an inverted population for incoherent dipoles. The optical information of hologram memory can be transferred to the whole brain during information processing. The integration of holography and QBD will provide us with a prospective approach in memory formation. Full article
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Article
The Prognostic and Predictive Significance of Tumor-Infiltrating Memory T Cells Is Reversed in High-Risk HNSCC
Cells 2022, 11(12), 1960; https://doi.org/10.3390/cells11121960 (registering DOI) - 17 Jun 2022
Abstract
Tumor-infiltrating CD45RO+ memory T cells have unanimously been described as a positive prognostic factor in head and neck squamous cell carcinomas (HNSCCs). Here, we investigated the long-term prognostic relevance of CD45RO+ memory T cells in HNSCC with special regard to the influence of [...] Read more.
Tumor-infiltrating CD45RO+ memory T cells have unanimously been described as a positive prognostic factor in head and neck squamous cell carcinomas (HNSCCs). Here, we investigated the long-term prognostic relevance of CD45RO+ memory T cells in HNSCC with special regard to the influence of clinical characteristics. Pre-treatment biopsy samples from 306 patients with predominantly advanced HNSCC were analyzed. Immunohistochemistry was used to stain tissue microarrays for CD45RO+ memory T cells. CD45RO cell densities were semi-automatically registered and used for survival analysis. High CD45RO+ cell densities were clearly associated with prolonged overall survival (OS) and recurrence-free survival as well as no evidence of disease status after 10 years (p < 0.05). In contrast, the prognostic significance of tumor-infiltrating memory T cells was completely reversed in high-risk groups: in poorly differentiated tumors (G3, G4) and in cases with lymph node involvement (N+), high memory T cell densities correlated with reduced 10-year OS (p < 0.05). In conclusion, an increased density of tumor-infiltrating CD45RO+ cells in HNSCC can be a positive as well as a negative prognostic factor, depending on disease stage and histological grade. Therefore, if CD45RO+ cell density is to be used as a prognostic biomarker, further clinical characteristics must be considered. Full article
(This article belongs to the Special Issue Cancer and Radiation Therapy)
Article
Pesticide Use and Associated Greenhouse Gas Emissions in Sugar Beet, Apples, and Viticulture in Austria from 2000 to 2019
Agriculture 2022, 12(6), 879; https://doi.org/10.3390/agriculture12060879 (registering DOI) - 17 Jun 2022
Abstract
The production of synthetic pesticides is energy intensive and can emit even more greenhouse gases (GHG) per kg than the production of synthetic fertilizers. However, this aspect is largely neglected when it comes to agriculture’s contribution to GHG emissions. Using official pesticide sales [...] Read more.
The production of synthetic pesticides is energy intensive and can emit even more greenhouse gases (GHG) per kg than the production of synthetic fertilizers. However, this aspect is largely neglected when it comes to agriculture’s contribution to GHG emissions. Using official pesticide sales data from Austria from 2000 to 2019, we analyzed (i) trends in insecticide, fungicide, and herbicide use and calculated production-related GHG emissions, and (ii) the share of pesticide-related versus fertilizer-related GHG emissions in three agricultural crops with different pesticide intensities: sugar beets, apples, and grapevines. We found that between 2000 and 2019, insecticide amounts increased by 58%, fungicide amounts increased by 29%, and herbicide amounts decreased by 29%; associated GHG emissions showed similar patterns. During the same period, acreage under conventional arable crops, orchards, and vineyards decreased by an average of 19%, indicating an increase in management intensity. In intensive apple production, GHG emissions associated with pesticide production and application accounted for 51% of total GHG emissions, in viticulture 37%, and in sugar beets 12%. We have shown that GHG emissions due to pesticide production and application can be significant, especially for pesticide-intensive crops. We therefore recommend that these pesticide-derived GHG emissions should also be attributed to the agricultural sector. Full article
Article
A Generic Formula and Some Special Cases for the Kullback–Leibler Divergence between Central Multivariate Cauchy Distributions
Entropy 2022, 24(6), 838; https://doi.org/10.3390/e24060838 (registering DOI) - 17 Jun 2022
Abstract
This paper introduces a closed-form expression for the Kullback–Leibler divergence (KLD) between two central multivariate Cauchy distributions (MCDs) which have been recently used in different signal and image processing applications where non-Gaussian models are needed. In this overview, the MCDs are surveyed and [...] Read more.
This paper introduces a closed-form expression for the Kullback–Leibler divergence (KLD) between two central multivariate Cauchy distributions (MCDs) which have been recently used in different signal and image processing applications where non-Gaussian models are needed. In this overview, the MCDs are surveyed and some new results and properties are derived and discussed for the KLD. In addition, the KLD for MCDs is showed to be written as a function of Lauricella D-hypergeometric series FD(p). Finally, a comparison is made between the Monte Carlo sampling method to approximate the KLD and the numerical value of the closed-form expression of the latter. The approximation of the KLD by Monte Carlo sampling method are shown to converge to its theoretical value when the number of samples goes to the infinity. Full article
(This article belongs to the Special Issue Information and Divergence Measures)
Technical Note
Theoretical Prediction of Gastrointestinal Absorption of Phytochemicals
Int. J. Plant Biol. 2022, 13(2), 163-179; https://doi.org/10.3390/ijpb13020016 (registering DOI) - 17 Jun 2022
Abstract
The discovery of bioactive compounds for non-invasive therapy has been the goal of research groups focused on pharmacotherapy. Phytonutrients have always been attractive for researchers because they are a significant source of bioactive phytochemicals. Still, it is challenging to determine which components show [...] Read more.
The discovery of bioactive compounds for non-invasive therapy has been the goal of research groups focused on pharmacotherapy. Phytonutrients have always been attractive for researchers because they are a significant source of bioactive phytochemicals. Still, it is challenging to determine which components show high biomedical activity and bioavailability after administration. However, based on the chemical structure of these phytochemicals, their physicochemical properties can be calculated to predict the probability of gastrointestinal (GI) absorption after oral administration. Indeed, different researchers have proposed several rules (e.g., Lipinski’s, Veber’s, Ghose’s, and Muegge’s rules) to attain these predictions, but only for synthetic compounds. Most phytochemicals do not fully comply with these rules even though they show high bioactivity and high GI absorption experimentally. Here, we propose a detailed methodology using scientifically validated web-based platforms to determine the physicochemical properties of five phytochemicals found in ginger, echinacea, and tobacco. Furthermore, we analyzed the calculated data and established a protocol based on the integration of these classical rules, plus other extended parameters, that we called the Phytochemical Rule, to obtain a more reliable prediction of the GI absorption of natural compounds. This methodology can help evaluate bioactive phytochemicals as potential drug candidates and predict their oral bioavailability in patients. Full article
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Article
Intracholecystic versus Intravenous Indocyanine Green (ICG) Injection for Biliary Anatomy Evaluation by Fluorescent Cholangiography during Laparoscopic Cholecystectomy: A Case–Control Study
J. Clin. Med. 2022, 11(12), 3508; https://doi.org/10.3390/jcm11123508 (registering DOI) - 17 Jun 2022
Abstract
(1) Background: Fluorescence cholangiography has been proposed as a method for improving the visualization and identification of extrahepatic biliary anatomy in order to possibly reduce injuries and related complications. The most common method of indocyanine green (ICG) administration is the intravenous route, whereas [...] Read more.
(1) Background: Fluorescence cholangiography has been proposed as a method for improving the visualization and identification of extrahepatic biliary anatomy in order to possibly reduce injuries and related complications. The most common method of indocyanine green (ICG) administration is the intravenous route, whereas evidence on direct ICG injection into the gallbladder is still quite limited. We aimed to compare the two different methods of ICG administration in terms of the visualization of extrahepatic biliary anatomy during laparoscopic cholecystectomy (LC), analyzing differences in the time of visualization, as well as the efficacy, advantages, and disadvantages of both modalities. (2) Methods: A total of 35 consecutive adult patients affected by acute or chronic gallbladder disease were enrolled in this prospective case–control study. Seventeen patients underwent LC with direct gallbladder ICG injection (IC-ICG) and eighteen subjects received intravenous ICG administration (IV-ICG). (3) Results: The groups were comparable with regard to their demographic and perioperative characteristics. The IV-ICG group had a significantly shorter overall operative time compared to the IC-ICG group (p = 0.017). IV-ICG was better at delineating the duodenum and the common hepatic duct compared to the IC-ICG method (p = 0.009 and p = 0.041, respectively). The cystic duct could be delineated pre-dissection in 76.5% and 66.7% of cases in the IC-ICG and IV-ICG group, respectively, and this increased to 88.2% and 83.3% after dissection. The common bile duct could be highlighted in 76.5% and 77.8% of cases in the IC-ICG and IV-ICG group, respectively. Liver fluorescence was present in one case in the IC-ICG group and in all cases after IV-ICG administration (5.8% versus 100%; p < 0.0001). (4) Conclusions: The present study demonstrates how ICG-fluorescence cholangiography can be helpful in identifying the extrahepatic biliary anatomy during dissection of Calot’s triangle in both administration methods. In comparison with intravenous ICG injection, the intracholecystic ICG route could provide a better signal-to-background ratio by avoiding hepatic fluorescence, thus increasing the bile duct-to-liver contrast. Full article
(This article belongs to the Special Issue Innovative Surgical Researches)
Review
Critical Review on Polylactic Acid: Properties, Structure, Processing, Biocomposites, and Nanocomposites
Materials 2022, 15(12), 4312; https://doi.org/10.3390/ma15124312 (registering DOI) - 17 Jun 2022
Abstract
Composite materials are emerging as a vital entity for the sustainable development of both humans and the environment. Polylactic acid (PLA) has been recognized as a potential polymer candidate with attractive characteristics for applications in both the engineering and medical sectors. Hence, the [...] Read more.
Composite materials are emerging as a vital entity for the sustainable development of both humans and the environment. Polylactic acid (PLA) has been recognized as a potential polymer candidate with attractive characteristics for applications in both the engineering and medical sectors. Hence, the present article throws lights on the essential physical and mechanical properties of PLA that can be beneficial for the development of composites, biocomposites, films, porous gels, and so on. The article discusses various processes that can be utilized in the fabrication of PLA-based composites. In a later section, we have a detailed discourse on the various composites and nanocomposites-based PLA along with the properties’ comparisons, discussing our investigation on the effects of various fibers, fillers, and nanofillers on the mechanical, thermal, and wear properties of PLA. Lastly, the various applications in which PLA is used extensively are discussed in detail. Full article
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Article
Effect of Encapsulated Ferrous Sulphate Fortified Salt on Hemoglobin Levels in Anemic Rats
Foods 2022, 11(12), 1795; https://doi.org/10.3390/foods11121795 (registering DOI) - 17 Jun 2022
Abstract
(1) Background: Iron deficiency anemia is a significant nutritional problem all over the world. Salt formulations supplemented with encapsulated iron and iodine (double-fortified) were tested for their efficacy in managing iron deficiency anemia. In this study, we have checked the effect of these [...] Read more.
(1) Background: Iron deficiency anemia is a significant nutritional problem all over the world. Salt formulations supplemented with encapsulated iron and iodine (double-fortified) were tested for their efficacy in managing iron deficiency anemia. In this study, we have checked the effect of these double-fortified salt formulations (iron and iodine) on hemoglobin (Hb) levels in anemic Wistar male rats. (2) Methods: The study was divided into two phases, viz., the development of anemia in the first phase and then the random division of anemic rats into five groups (Groups A to E). These rats were fed with three different salt formulations (Groups A to C); Group D was continued on a low iron diet, and Group E was on a normal pellet diet over a period of 84 days. The level of Hb was tested in each group. (3) Results: The rats in Groups A, B, C, and E recovered from anemia significantly, with higher Hb levels. On day 84, however, the Hb level in Group D continued to decrease. The bodyweight of the rats was not affected in any way. In all of the groups, histopathology examinations in various organs revealed no significant changes. (4) Conclusions: All of the three different salt formulations showed significant recovery in the anemic rats as compared to the rats fed with a normal pelleted diet. Full article
(This article belongs to the Special Issue Current Research on Vitamin and Mineral Fortification in Foods)
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Article
The Analysis of Arterial Stiffness in Heart Failure Patients: The Prognostic Role of Pulse Wave Velocity, Augmentation Index and Stiffness Index
J. Clin. Med. 2022, 11(12), 3507; https://doi.org/10.3390/jcm11123507 (registering DOI) - 17 Jun 2022
Abstract
Background: The role of arterial stiffness in the pathogenesis and clinical outcome of heart failure (HF) patients has to be clarified. The aim of this study was to evaluate the prognostic role of arterial stiffness in HF patients discharged after acute episode of [...] Read more.
Background: The role of arterial stiffness in the pathogenesis and clinical outcome of heart failure (HF) patients has to be clarified. The aim of this study was to evaluate the prognostic role of arterial stiffness in HF patients discharged after acute episode of decompensation by evaluating cut-off values for clinical assessment. Methods: Patients admitted for decompensated heart failure (ADHF) underwent pre-discharge evaluation. Arterial stiffness was measured by aortic pulse wave velocity (aPWV), augmentation index (AIx75) and stiffness index (β0). Patients were also evaluated after discharge for a variable follow-up time. Results: We observed 199 patients (male 61.3%, age 76.2 ± 10.7 years) after discharge for a median of 437 days (IQR 247-903), 69 (34.7%) patients suffered HF with preserved ejection fraction (HFpEF), 45 (22.6%) patients experienced HF with mid-range ejection fraction (HFmEF) and 85 (42.7%) reported an HF with reduced ejection fraction (HFrEF). After the adjustment for principal confounders, aPWV, AIx75 and β0 were inversely correlated with free-event survival (p = 0.006, p < 0.001, p = 0.001): only β0 was inversely correlated with overall survival (p = 0.03). Analysing the threshold, overall survival was inversely correlated with β0 ≥3 (HR 2.1, p = 0.04) and free-event survival was inversely correlated with aPWV ≥10 m/s (HR 1.7, p = 0.03), AIx75 ≥ 25 (HR 2.4, p < 0.001), and β0 ≥ 3 (HR 2.0, p = 0.009). Dividing HF patients for LV ejection fraction, β0 and AIx75 appeared to be accurate prognostic predictors among the three different classes according to free-event survival. Conclusions: The non-invasive measurements of arterial stiffness proved to be strong prognostic parameters in HF patients discharged after an acute HF decompensation. Full article
(This article belongs to the Special Issue Advances and Perspectives in Heart Failure)
Article
Identification of Phage Receptor-Binding Protein Sequences with Hidden Markov Models and an Extreme Gradient Boosting Classifier
Viruses 2022, 14(6), 1329; https://doi.org/10.3390/v14061329 (registering DOI) - 17 Jun 2022
Abstract
Receptor-binding proteins (RBPs) of bacteriophages initiate the infection of their corresponding bacterial host and act as the primary determinant for host specificity. The ever-increasing amount of sequence data enables the development of predictive models for the automated identification of RBP sequences. However, the [...] Read more.
Receptor-binding proteins (RBPs) of bacteriophages initiate the infection of their corresponding bacterial host and act as the primary determinant for host specificity. The ever-increasing amount of sequence data enables the development of predictive models for the automated identification of RBP sequences. However, the development of such models is challenged by the inconsistent or missing annotation of many phage proteins. Recently developed tools have started to bridge this gap but are not specifically focused on RBP sequences, for which many different annotations are available. We have developed two parallel approaches to alleviate the complex identification of RBP sequences in phage genomic data. The first combines known RBP-related hidden Markov models (HMMs) from the Pfam database with custom-built HMMs to identify phage RBPs based on protein domains. The second approach consists of training an extreme gradient boosting classifier that can accurately discriminate between RBPs and other phage proteins. We explained how these complementary approaches can reinforce each other in identifying RBP sequences. In addition, we benchmarked our methods against the recently developed PhANNs tool. Our best performing model reached a precision-recall area-under-the-curve of 93.8% and outperformed PhANNs on an independent test set, reaching an F1-score of 84.0% compared to 69.8%. Full article
(This article belongs to the Special Issue Virus Bioinformatics 2022)
Article
A Qualitative Study on the Design and Implementation of the National Action Plan on Antimicrobial Resistance in the Philippines
Antibiotics 2022, 11(6), 820; https://doi.org/10.3390/antibiotics11060820 (registering DOI) - 17 Jun 2022
Abstract
Antimicrobial resistance (AMR) is a global public health threat that warrants urgent attention. Countries developed their national action plans (NAPs) following the launch of the Global Action Plan on AMR in 2015. The development and implementation of NAPs are often complicated due to [...] Read more.
Antimicrobial resistance (AMR) is a global public health threat that warrants urgent attention. Countries developed their national action plans (NAPs) following the launch of the Global Action Plan on AMR in 2015. The development and implementation of NAPs are often complicated due to the multifaceted nature of AMR, and studies analyzing these aspects are lacking. We analyzed the development and implementation of the Philippine NAP on AMR with guidance from an AMR governance framework. We conducted in-depth interviews with 37 participants across the One Health spectrum. The interviews were transcribed verbatim and were analyzed thematically, adopting an interpretative approach. The enabling factors for NAP implementation include (1) a high level of governmental support and involvement of relevant stakeholders, (2) the development of policies to support improved responses in infection prevention and control and antimicrobial stewardship, and (3) better engagement and advocacy by professional associations and civil society groups. The challenges include (1) a lack of resources and regulatory capacity, (2) insufficient impetus for AMR research and surveillance, and (3) limited One Health engagement. Although there has been considerable progress for human health, strengthening the involvement and representation of the animal health and environment sectors in the AMR scene must be undertaken. Developing well-defined roles within policies will be paramount to the strong implementation of AMR strategies. Full article
Article
Vibro-Acoustic Modelling of Aeronautical Panels Reinforced by Unconventional Stiffeners
Aerospace 2022, 9(6), 327; https://doi.org/10.3390/aerospace9060327 (registering DOI) - 17 Jun 2022
Abstract
The purpose of this work is to characterise the vibro-acoustic behaviour of rectangular flat panels reinforced by “unconventional” stiffeners. Such panels are being increasingly employed in the aircraft industry in the case of composite fuselage, so that the assessment of the most efficient [...] Read more.
The purpose of this work is to characterise the vibro-acoustic behaviour of rectangular flat panels reinforced by “unconventional” stiffeners. Such panels are being increasingly employed in the aircraft industry in the case of composite fuselage, so that the assessment of the most efficient and accurate numerical techniques and modelling procedures to correctly predict their dynamic and acoustic behaviour is required. To this end, an analytical method, available from literature, has been initially employed to investigate on the main attributes of sound transmission loss properties of stiffened panels driven by an acoustic diffuse field excitation. Based on existing commercial codes, different numerical techniques have been implemented and deeply examined to assess their potentiality and restrictions. Among them, the Hybrid method has been eventually identified as the best compromise in terms of accuracy and computational effort. The drawbacks of deterministic and even Hybrid numerical approaches for medium–high frequency vibro-acoustic analysis when dealing with large structures, make use of the pure SEA approach compulsory. In particular, a refined tuning of a specific feature made available within the employed SEA analysis environment when dealing with reinforced shells is implemented as a potential solution to overcome the complexity in correctly modelling the examined unconventionally stiffened panels. Full article
(This article belongs to the Special Issue Advances in Aerospace Sciences and Technology III)
Study Protocol
Psychological Intervention in Women Victims of Childhood Sexual Abuse: An Open Study—Protocol of a Randomized Controlled Clinical Trial Comparing EMDR Psychotherapy and Trauma-Based Cognitive Therapy
Int. J. Environ. Res. Public Health 2022, 19(12), 7468; https://doi.org/10.3390/ijerph19127468 (registering DOI) - 17 Jun 2022
Abstract
Introduction: Most victims of sexual abuse have symptoms that may lead to post-traumatic stress disorder. This study aims to offer evidence-based psychological treatment to women who have been sexually abused earlier in life and currently have sequelae from that trauma. With this treatment, [...] Read more.
Introduction: Most victims of sexual abuse have symptoms that may lead to post-traumatic stress disorder. This study aims to offer evidence-based psychological treatment to women who have been sexually abused earlier in life and currently have sequelae from that trauma. With this treatment, each of the women in the study will hopefully improve their overall quality of life and, more specifically, it is expected that post-traumatic stress symptoms will decrease, as found in recent studies, as well as strengthening their security, confidence, and coping with the situations they have experienced. Methods and analysis: The effect of two therapeutic approaches focused on the improvement of trauma will be evaluated in a sample of 30–50 women victims of childhood sexual abuse, with a randomized clinical trial comparing EMDR psychotherapy and trauma-focused cognitive behavioral therapy. According to the literature reviewed, both approaches will considerably improve self-esteem when the appropriate number of sessions are conducted, significantly reducing general psychiatric symptoms and depression. Furthermore, the effects are sustained over time. It should be noted that this study will be carried out comparing both therapies, analyzing both the differential benefit of each and the cumulative effect of receiving both treatments and in which order. It is also intended to demonstrate that implementing the protocols presented in this study will help improve the quality of life of the women who benefit from them, and after this study, it will be possible to replicate this program in other people with the same problems. Each of the therapeutic benefits of each of them will be analyzed, and clinical and logistical guidance will be provided to implement both, including a session-by-session protocol. Full article
(This article belongs to the Special Issue Interventions after Traumatic Events)
Systematic Review
Response to Systemic Therapies in Ovarian Adult Granulosa Cell Tumors: A Literature Review
Cancers 2022, 14(12), 2998; https://doi.org/10.3390/cancers14122998 (registering DOI) - 17 Jun 2022
Abstract
For adult granulosa cell tumors (aGCTs), the preferred treatment modality is surgery. Chemotherapy and anti-hormonal therapy are also frequently used in patients with recurrent aGCT. We aimed to review the existing literature on the response to chemotherapy and anti-hormonal therapy in patients with [...] Read more.
For adult granulosa cell tumors (aGCTs), the preferred treatment modality is surgery. Chemotherapy and anti-hormonal therapy are also frequently used in patients with recurrent aGCT. We aimed to review the existing literature on the response to chemotherapy and anti-hormonal therapy in patients with aGCT. Embase and MEDLINE were searched from inception to November 2021 for eligible studies. Objective response rate (ORR) was calculated as the total number of cases with a complete response (CR) or a partial response (PR). Disease control rate (DCR) was defined as the sum of cases with CR, PR or stable disease (SD). A total of 10 studies were included that reported on chemotherapy and 13 studies were included that reported on anti-hormonal therapy. The response rates of the 56 chemotherapy regimens that could be evaluated resulted in an ORR of 30% and DCR of 58%. For anti-hormonal therapy, the results of 73 regimens led to an ORR of 11% and a DCR of 66%. Evidence on systemic therapy in aGCT only is limited. For both chemotherapy and anti-hormonal therapy, the ORR is limited, but the response is considerably higher when patients achieving SD are included. New approaches are needed to provide more evidence and standardize treatment in aGCT. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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Article
Fabrication and Properties of Tree-Branched Cellulose Nanofibers (CNFs) via Acid Hydrolysis Assisted with Pre-Disintegration Treatment
Nanomaterials 2022, 12(12), 2089; https://doi.org/10.3390/nano12122089 (registering DOI) - 17 Jun 2022
Abstract
In this paper, the novel morphology of cellulose nanofibers (CNFs) with a unique tree-branched structure was discovered by using acid hydrolysis assisted with pre-disintegration treatment from wood pulps. For comparison, the pulps derived from both softwood and hardwood were utilized to extract nanocellulose [...] Read more.
In this paper, the novel morphology of cellulose nanofibers (CNFs) with a unique tree-branched structure was discovered by using acid hydrolysis assisted with pre-disintegration treatment from wood pulps. For comparison, the pulps derived from both softwood and hardwood were utilized to extract nanocellulose in order to validate the feasibility of proposed material fabrication technique. The morphology, crystalline structures, chemical structures, and thermal stability of nanocellulose were characterized by means of transmission electron microscopy (TEM), X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FTIR), as well as thermogravimetric analysis (TGA). Prior to acid hydrolysis, softwood and hardwood pulps underwent the disintegration treatment in the fiber dissociator. It has been found that nanocellulose derived from disintegrated pulps possesses much longer fiber length (approximately 5–6 μm) and more evident tree-branched structures along with lower degree of crystallinity when compared with those untreated counterparts. The maximum mass loss rate of CNFs takes place at the temperature level of approximately 225 °C, and appears to be higher than that of cellulose nanowhiskers (CNWs), which might be attributed to an induced impact of amorphous content. On the other hand, disintegration treatment is quite beneficial to the enhancement of tensile strength of nanocellulose films. This study elaborates a new route of material fabrication toward the development of well-tailored tree-branched CNFs in order to broaden the potential widespread applications of nanocellulose with diverse morphological structures. Full article
(This article belongs to the Special Issue From Biomass to Nanomaterials)
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Article
Satellite-Based Monitoring of Coastal Wetlands in Yancheng, Jiangsu Province, China
J. Mar. Sci. Eng. 2022, 10(6), 829; https://doi.org/10.3390/jmse10060829 (registering DOI) - 17 Jun 2022
Abstract
The dynamic process of the wetland can reflect its impact on the environment, and finding a balance point supporting harmonious coexistence between man and nature has become an issue of increasing concern. On the basis of previous studies that have focused on local [...] Read more.
The dynamic process of the wetland can reflect its impact on the environment, and finding a balance point supporting harmonious coexistence between man and nature has become an issue of increasing concern. On the basis of previous studies that have focused on local coastal wetlands, the temporal and spatial changes and driving forces of wetlands in the Yancheng coastal area from 1991 to 2021 were analyzed over a larger area. According to the study findings: (1) The results of the study of the Yancheng coastal wetland with a larger scope differed significantly from findings resulting from a study of coastal wetland only. This difference was mainly reflected in the relatively stable situation of wetland ecology as a whole, while the changes in local surface features were more significant. (2) Natural wetlands were transformed into artificial wetlands and non-wetland types, and artificial wetlands were transformed into non-wetland types; additionally, reverse transformations and internal transformations of surface features also took place. For instance, the saltpan was transformed into mudflats (86.26 km2), and some mudflats into herbaceous vegetation (193.47 km2). (3) When analyzing the impact intensity of human activities on the Yancheng wetland, it was found that this factor has experienced a process of first rising and then falling. The index was 0.650, 0.653, 0.664, 0.661, and 0.641 in 1991, 2000, 2008, 2016, and 2021, respectively. (4) Lastly, an analysis of factors driving wetland change revealed that human factors were the most critical reasons for wetland landscape change. Our work can play a reference and inspiration role in the monitoring and protection of similar coastal wetlands. Full article
Article
Magnéli TiO2 as a High Durability Support for the Proton Exchange Membrane (PEM) Fuel Cell Catalysts
Energies 2022, 15(12), 4437; https://doi.org/10.3390/en15124437 (registering DOI) - 17 Jun 2022
Abstract
Proton exchange membrane fuel cells (PEMFCs) cathode catalysts’ robustness is one of the primary factors determining its long-term performance and durability. This work presented a new class of corrosion-resistant catalyst, Magnél TiO2 supported Pt (Pt/Ti9O17) composite, synthesized. The [...] Read more.
Proton exchange membrane fuel cells (PEMFCs) cathode catalysts’ robustness is one of the primary factors determining its long-term performance and durability. This work presented a new class of corrosion-resistant catalyst, Magnél TiO2 supported Pt (Pt/Ti9O17) composite, synthesized. The durability of a Pt/Ti9O17 cathode under the PEMFC operating protocol was evaluated and compared with the state-of-the-art Pt/C catalyst. Like Pt/C, Pt/Ti9O17 exhibited exclusively 4e- oxygen reduction reaction (ORR) in the acidic solution. The accelerated stress tests (AST) were performed using Pt/Ti9O17 and Pt/C catalysts in an O2-saturated 0.5 M H2SO4 solution using the potential-steps cycling experiments from 0.95 V to 0.6 V for 12,000 cycles. The results indicated that the electrochemical surface area (ECSA) of the Pt/Ti9O17 is significantly more stable than that of the state-of-the-art Pt/C, and the ECSA loss after 12,000 potential cycles is only 10 ± 2% for Pt/Ti9O17 composite versus 50 ± 5% for Pt/C. Furthermore, the current density and onset potential at the ORR polarization curve at Pt/C were significantly affected by the AST test. In contrast, the same remained almost constant at the modified electrode, Pt/Ti9O17. This demonstrated the excellent stability of Pt nanoparticles supported on Ti9O17. Full article
(This article belongs to the Special Issue Advances in Electrochemical Energy System)

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