The 2023 MDPI Annual Report has
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14 pages, 267 KiB  
Article
Evaluation of Whole Genome Sequencing-Based Predictions of Antimicrobial Resistance to TB First Line Agents: A Lesson from 5 Years of Data
by Meenu Kaushal Sharma, Michael Stobart, Pierre-Marie Akochy, Heather Adam, Debra Janella, Melissa Rabb, Mohey Alawa, Inna Sekirov, Gregory J. Tyrrell and Hafid Soualhine
Int. J. Mol. Sci. 2024, 25(11), 6245; https://doi.org/10.3390/ijms25116245 - 6 Jun 2024
Abstract
Phenotypic susceptibility testing of the Mycobacterium tuberculosis complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). [...] Read more.
Phenotypic susceptibility testing of the Mycobacterium tuberculosis complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials—isoniazid, rifampin, ethambutol, and pyrazinamide—for MTBC isolates tested between the years 2018–2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid, rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid, rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks. Full article
14 pages, 4461 KiB  
Article
Novel Lipid Nanocomplex Co-Carrying Bcl2 siRNA and Quantum Dots for EGF Receptor-Targeted Anti-Cancer Theranosis
by Moon Jung Choi, Seong Jae Kang, Yeon Kyung Lee, Kang Chan Choi, Do Hyun Lee, Hwa Yeon Jeong, Min Woo Kim, Keun Sik Kim and Yong Serk Park
Int. J. Mol. Sci. 2024, 25(11), 6246; https://doi.org/10.3390/ijms25116246 - 6 Jun 2024
Abstract
Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood–immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the [...] Read more.
Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood–immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis. Full article
(This article belongs to the Special Issue Targeted Delivery of Nucleic Acids)
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12 pages, 3444 KiB  
Article
Bimetallic Perthiocarbonate Complexes of Cobalt: Synthesis, Structure and Bonding
by Alaka Nanda Pradhan, Shivankan Mishra, Urminder Kaur, Bikram Keshari Rout, Jean-François Halet and Sundargopal Ghosh
Molecules 2024, 29(11), 2688; https://doi.org/10.3390/molecules29112688 - 6 Jun 2024
Abstract
The syntheses and structural elucidation of bimetallic thiolate complexes of early and late transition metals are described. Thermolysis of the bimetallic hydridoborate species [{Cp*CoPh}{µ-TePh}{µ-TeBH3-ĸ2Te,H}{Cp*Co}] (Cp* = ɳ5-C5Me5) ( [...] Read more.
The syntheses and structural elucidation of bimetallic thiolate complexes of early and late transition metals are described. Thermolysis of the bimetallic hydridoborate species [{Cp*CoPh}{µ-TePh}{µ-TeBH3-ĸ2Te,H}{Cp*Co}] (Cp* = ɳ5-C5Me5) (1) in the presence of CS2 afforded the bimetallic perthiocarbonate complex [(Cp*Co)2(μ-CS4-κ1S:κ2S′)(μ-S2-κ2S″:κ1S‴)] (2) and the dithiolene complex [(Cp*Co)(μ-C3S5-κ1S,S′] (3). Complex 2 contains a four-membered metallaheterocycle (Co2S2) comprising a perthiocarbonate [CS4]2− unit and a disulfide [S2]2− unit, attached opposite to each other. Complex 2 was characterized by employing different multinuclear NMR, infrared spectroscopy, mass spectrometry, and single-crystal X-ray diffraction studies. Preliminary studies show that [Cp*VCl2]3 (4) with an intermediate generated from CS2 and [LiBH4·THF] yielded thiolate species, albeit different from the cobalt system. Furthermore, a computational analysis was performed to provide insight into the bonding of this bimetallic perthiocarbonate complex. Full article
(This article belongs to the Special Issue Exclusive Feature Papers in Inorganic Chemistry 2.0)
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12 pages, 880 KiB  
Article
An Attempt to Replace Pure Citric Acid with Natural Lemon Juice during Potato Starch Esterification
by Ewa Tomaszewska-Ciosk, Ewa Zdybel, Małgorzata Kapelko-Żeberska, Bartosz Raszewski, Krzysztof Buksa, Agnieszka Maj, Tomasz Zięba and Artur Gryszkin
Molecules 2024, 29(11), 2687; https://doi.org/10.3390/molecules29112687 - 6 Jun 2024
Abstract
The application of chemical operations in food processing, in which pure chemical compounds are used to modify food ingredients, often raises social concerns. One of the most frequently modified dietary substances is starch, e.g., E1401–E1404, E1412–E1414, E1420, E1422, E1440, E1442, and E1450–E1452. An [...] Read more.
The application of chemical operations in food processing, in which pure chemical compounds are used to modify food ingredients, often raises social concerns. One of the most frequently modified dietary substances is starch, e.g., E1401–E1404, E1412–E1414, E1420, E1422, E1440, E1442, and E1450–E1452. An alternative solution to chemical treatments seems to be the use of raw materials naturally containing substrates applied for starch modification. Heating starch with a lemon juice concentrate can be considered a novel and effective method for producing starch citrate, which is part of the so-called “green chemistry”. The modified preparations obtained as a result of potato starch esterification with natural lemon juice had a comparable degree of esterification to that of the esters produced with pure citric acid. In addition, the use of the juice doubled their resistance to amylolytic enzymes compared to the preparations made with pure acid. Replacing citric acid with lemon juice can facilitate the esterification process, and the analyzed properties of both types of modified preparations indicate that starch esters produced with pure citric acid can be successfully replaced by those produced using natural lemon juice, which may increase the social acceptance of these modified preparations. Full article
(This article belongs to the Special Issue Food Polysaccharides: Structure, Properties and Application II)
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15 pages, 5618 KiB  
Article
Thermal Stability of Dispersions of Amino-Functionalized Silica in Glycol and in 50–50 Aqueous Glycol
by Marta Kalbarczyk, Sebastian Skupiński and Marek Kosmulski
Molecules 2024, 29(11), 2686; https://doi.org/10.3390/molecules29112686 - 6 Jun 2024
Abstract
Dispersions of amino-functionalized silica in ethylene glycol (EG) and in aqueous glycol show excellent stability at room temperature. Stability at elevated temperatures would be much desired with respect to their potential application as heat-transfer fluids. Amino-functionalized silica was dispersed in EG and in [...] Read more.
Dispersions of amino-functionalized silica in ethylene glycol (EG) and in aqueous glycol show excellent stability at room temperature. Stability at elevated temperatures would be much desired with respect to their potential application as heat-transfer fluids. Amino-functionalized silica was dispersed in EG and in 50–50 aqueous EG by mass. HCl and acetic acid were added to enhance the positive ζ potential. The dispersions were stored at 40, 60, 80, and 100 °C for up to 28 days, and ζ potential and apparent particle radius were studied as a function of elapsed time. The particles showed a positive ζ potential in excess of 40 mV (Smoluchowski), which remained unchanged for 28 days. Such a high absolute value of ζ potential is sufficient to stabilize the dispersion against flocculation and sedimentation. The apparent particle radius in acidified dispersions was about 70 nm, and it was stable for 28 days. The particles were larger in pH-neutral dispersions. The apparent particle radius was about 80 nm in fresh dispersions and it increased on long storage at 80 and 100 °C. Full article
(This article belongs to the Section Physical Chemistry)
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11 pages, 5576 KiB  
Article
Chalcogen-Bond-Assisted Formation of the N→C Dative Bonds in the Complexes between Chalcogenadiazoles/Chalcogenatriazoles and Fullerene C60
by Yu Zhang and Weizhou Wang
Molecules 2024, 29(11), 2685; https://doi.org/10.3390/molecules29112685 - 6 Jun 2024
Abstract
The existence of the N→C dative bonds in the complexes between N-containing molecules and fullerenes have been verified both theoretically and experimentally. However, finding stable N→C dative bonds is still a highly challenging task. In this work, we investigated computationally the N→C dative [...] Read more.
The existence of the N→C dative bonds in the complexes between N-containing molecules and fullerenes have been verified both theoretically and experimentally. However, finding stable N→C dative bonds is still a highly challenging task. In this work, we investigated computationally the N→C dative bonds in the complexes formed by fullerene C60 with 1,2,5-chalcogenadiazoles, 2,1,3-benzochalcogenadiazoles, and 1,2,4,5-chalcogenatriazoles, respectively. It was found that the N→C dative bonds are formed along with the formation of the N–Ch···C (Ch = S, Se, Te) chalcogen bonds. In the gas phase, from S-containing complexes through Se-containing complexes to Te-containing complexes, the intrinsic interaction energies become more and more negative, which indicates that the N–Ch···C chalcogen bonds can facilitate the formation of the N→C dative bonds. The intrinsic interaction energies are compensated by the large deformation energy of fullerene C60. The total interaction energies of Te-containing complexes are negative, while both total interaction energies of the S-containing complexes and Se-containing complexes are positive. This means that the N→C dative bonds in the Te-containing complexes are more easily observed in experiments in comparison with those in the S-containing complexes and Se-containing complexes. This study provides a new theoretical perspective on the experimental observation of the N→C dative bonds in complexes involving fullerenes. Further, the formation of stable N→C dative bonds in the complexes involving fullerenes can significantly change the properties of fullerenes, which will greatly simulate and expand the application range of fullerenes. Full article
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11 pages, 588 KiB  
Study Protocol
Factors Influencing Dementia Care Competence among Care Staff: A Mixed-Methods Systematic Review Protocol
by Jinfeng Zhu, Jing Wang, Bo Zhang, Xi Zhang and Hui Wu
Healthcare 2024, 12(11), 1155; https://doi.org/10.3390/healthcare12111155 (registering DOI) - 6 Jun 2024
Abstract
Background: Dementia care competence is defined as the ability, acquired through practical experience, to deliver high-quality care services to persons with dementia (PWD). However, many studies only focus on one aspect of competence using qualitative or quantitative research design and have small sample [...] Read more.
Background: Dementia care competence is defined as the ability, acquired through practical experience, to deliver high-quality care services to persons with dementia (PWD). However, many studies only focus on one aspect of competence using qualitative or quantitative research design and have small sample sizes of care staff with dementia. This study aims to conduct a mixed-methods systematic review of the factors influencing the competence of dementia care staff, and explore the relationship between these factors and competence. Methods: This review was designed following the PRISMA-P 2015 statement and methodological guidance for the conduct of mixed-methods systematic reviews from the Joanna Briggs Institute (JBI). Seven English and four Chinese databases will be searched to systematically review the existing eligible studies. JBI Critical Appraisal Checklist for Qualitative Research and Analytical Cross-Sectional Studies will be used to assess the methodological quality of each study. A JBI Mixed-Methods Data Extraction Form will be applied for data extraction. The JBI convergent integrated approach will be used for data synthesis and integration. The synthesized findings will be graded according to the JBI ConQual approach as high, moderate, low, or very low. The protocol was registered with PROSPERO in October 2023 (CRD42023474093). Full article
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14 pages, 9296 KiB  
Article
Combination of an Optically Induced Dielectrophoresis (ODEP) Mechanism and a Laminar Flow Pattern in a Microfluidic System for the Continuous Size-Based Sorting and Separation of Microparticles
by Po-Yu Chu, Ai-Yun Wu, Kun-Yu Tsai, Chia-Hsun Hsieh and Min-Hsien Wu
Biosensors 2024, 14(6), 297; https://doi.org/10.3390/bios14060297 (registering DOI) - 6 Jun 2024
Abstract
Optically induced dielectrophoresis (ODEP)-based microparticle sorting and separation is regarded as promising. However, current methods normally lack the downstream process for the transportation and collection of separated microparticles, which could limit its applications. To address this issue, an ODEP microfluidic chip encompassing three [...] Read more.
Optically induced dielectrophoresis (ODEP)-based microparticle sorting and separation is regarded as promising. However, current methods normally lack the downstream process for the transportation and collection of separated microparticles, which could limit its applications. To address this issue, an ODEP microfluidic chip encompassing three microchannels that join only at the central part of the microchannels (i.e., the working zone) was designed. During operation, three laminar flows were generated in the zone, where two dynamic light bar arrays were designed to sort and separate PS (polystyrene) microbeads of different sizes in a continuous manner. The separated PS microbeads were then continuously transported in laminar flows in a partition manner for the final collection. The results revealed that the method was capable of sorting and separating PS microbeads in a high-purity manner (e.g., the microbead purity values were 89.9 ± 3.7, 88.0 ± 2.5, and 92.8 ± 6.5% for the 5.8, 10.8, and 15.8 μm microbeads harvested, respectively). Overall, this study demonstrated the use of laminar flow and ODEP to achieve size-based sorting, separation, and collection of microparticles in a continuous and high-performance manner. Apart from the demonstration, this method can also be utilized for size-based sorting and the separation of other biological or nonbiological microparticles. Full article
(This article belongs to the Section Optical and Photonic Biosensors)
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15 pages, 4692 KiB  
Article
Design, Synthesis, and Cytotoxic Assessment of New Haloperidol Analogues as Potential Anticancer Compounds Targeting Sigma Receptors
by Daniele Zampieri, Maurizio Romano, Sara Fortuna, Emanuele Amata, Maria Dichiara, Giuseppe Cosentino, Agostino Marrazzo and Maria Grazia Mamolo
Molecules 2024, 29(11), 2697; https://doi.org/10.3390/molecules29112697 (registering DOI) - 6 Jun 2024
Abstract
Sigma receptors (SRs), including SR1 and SR2 subtypes, have attracted increasing interest in recent years due to their involvement in a wide range of activities, including the modulation of opioid analgesia, neuroprotection, and potential anticancer activity. In this context, haloperidol (HAL), a commonly [...] Read more.
Sigma receptors (SRs), including SR1 and SR2 subtypes, have attracted increasing interest in recent years due to their involvement in a wide range of activities, including the modulation of opioid analgesia, neuroprotection, and potential anticancer activity. In this context, haloperidol (HAL), a commonly used antipsychotic drug, also possesses SR activity and cytotoxic effects. Herein, we describe the identification of novel SR ligands, obtained by a chemical hybridization approach. There wereendowed with pan-affinity for both SR subtypes and evaluated their potential anticancer activity against SH-SY5Y and HUH-7 cancer cell lines. Through a chemical hybridization approach, we identified novel compounds (4d, 4e, 4g, and 4j) with dual affinity for SR1 and SR2 receptors. These compounds were subjected to cytotoxicity testing using a resazurin assay. The results revealed potent cytotoxic effects against both cancer cell lines, with IC50 values comparable to HAL. Interestingly, the cytotoxic potency of the novel compounds resembled that of the SR1 antagonist HAL rather than the SR2 agonist siramesine (SRM), indicating the potential role of SR1 antagonism in their mechanism of action. The further exploration of their structure-activity relationships and their evaluation in additional cancer cell lines will elucidate their therapeutic potential and may pave the way for the development of novel anticancer agents that target SRs. Full article
(This article belongs to the Special Issue Small Molecules in Targeted Cancer Therapy)
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27 pages, 4080 KiB  
Review
Satellite Remote Sensing Tools for Drought Assessment in Vineyards and Olive Orchards: A Systematic Review
by Nazaret Crespo, Luís Pádua, João A. Santos and Helder Fraga
Remote Sens. 2024, 16(11), 2040; https://doi.org/10.3390/rs16112040 (registering DOI) - 6 Jun 2024
Abstract
Vineyards and olive groves are two of the most important Mediterranean crops, not only for their economic value but also for their cultural and environmental significance, playing a crucial role in global agriculture. This systematic review, based on an adaptation of the 2020 [...] Read more.
Vineyards and olive groves are two of the most important Mediterranean crops, not only for their economic value but also for their cultural and environmental significance, playing a crucial role in global agriculture. This systematic review, based on an adaptation of the 2020 PRISMA statement, focuses on the use of satellite remote sensing tools for the detection of drought in vineyards and olive groves. This methodology follows several key steps, such as defining the approach, selecting keywords and databases, and applying exclusion criteria. The bibliometric analysis revealed that the most frequently used terms included “Google Earth Engine” “remote sensing” “leaf area index” “Sentinel-2”, and “evapotranspiration”. The research included a total of 81 articles published. The temporal distribution shows an increase in scientific production starting in 2018, with a peak in 2021. Geographically, the United States, Italy, Spain, France, Tunisia, Chile, and Portugal lead research in this field. The studies were classified into four categories: aridity and drought monitoring (ADM), agricultural water management (AWM), land use management (LUM), and water stress (WST). Research trends were analysed in each category, highlighting the use of satellite platforms and sensors. Several case studies illustrate applications in vineyards and olive groves, especially in semi-arid regions, focusing on the estimation of evapotranspiration, crop coefficients, and water use efficiency. This article provides a comprehensive overview of the current state of research on the use of satellite remote sensing for drought assessment in grapevines and olive trees, identifying trends, methodological approaches, and opportunities for future research in this field. Full article
(This article belongs to the Special Issue Remote Sensing in Viticulture II)
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14 pages, 7752 KiB  
Article
Effect of Green Infrastructure with Different Woody Plant Root Systems on the Reduction of Runoff Nitrogen
by Bei Zhang, Liang Chen and Taolve Gao
Water 2024, 16(11), 1628; https://doi.org/10.3390/w16111628 (registering DOI) - 6 Jun 2024
Abstract
Rainfall-runoff nitrogen (N) pollution has emerged as the primary source of water contamination due to rapid urbanization. Green infrastructure (GI), as the representative measure, is widely used in controlling N pollution in runoff. However, there is limited research on the impact of woody [...] Read more.
Rainfall-runoff nitrogen (N) pollution has emerged as the primary source of water contamination due to rapid urbanization. Green infrastructure (GI), as the representative measure, is widely used in controlling N pollution in runoff. However, there is limited research on the impact of woody plants on N reduction in GIs. Therefore, this study aimed to investigate the influence and relationship of Sophora japonica (with tap root) and Malus baccata (with fibrous root) on N removal in GIs. Utilizing the advanced root analysis software WinRHIZO (version 4.0b), a meticulous examination of the morphological traits of plant roots was conducted. The findings unveiled a striking contrast between the root systems of two species: S. japonica primarily boasts a vertically oriented root configuration, whereas M. baccata’s root system is characterized by an extensively lateral, or horizontal, growth pattern. Specifically, in comparison to S. japonica, the horizontal roots of M. baccata demonstrated a substantial superiority, with their total root length measuring 10.95 times longer, the surface area spanning 6.25 times wider, and the cumulative volume being 3.93 times greater. For comparing the load reduction rates on runoff NH3-N, NO3-N, and TN of the different root morphologies’ GIs, S. japonica GI had the highest purification effect on the three pollutants, and the average load reduction rates of three pollutants reached 67.74%, 33.83%, and 38.96%, respectively, which were 11.42%, 27.46%, and 6.16% higher than those of the control. The variance contribution rate of vertical root and horizontal root characteristics on runoff nitrogen load reduction accounted for 86.47% of the total root contribution rate. The volume of vertical roots emerged as the most crucial characteristic factor affecting the reduction of N load. Full article
(This article belongs to the Section Urban Water Management)
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11 pages, 610 KiB  
Article
Cropping Flax for Grain and Fiber: A Case-Study from Italy
by Piernicola Masella, Giulia Angeloni and Incoronata Galasso
Biomass 2024, 4(2), 599-609; https://doi.org/10.3390/biomass4020032 (registering DOI) - 6 Jun 2024
Abstract
Flax (Linum usitatissimum L.) can be grown both as an oil crop and as a fiber crop, and this offers new opportunities when included in the framework of a whole-crop biorefinery, a system in which a range of products are made from [...] Read more.
Flax (Linum usitatissimum L.) can be grown both as an oil crop and as a fiber crop, and this offers new opportunities when included in the framework of a whole-crop biorefinery, a system in which a range of products are made from portions of grain and straw and in which both of these should be satisfactorily produced. In the present experiment, the effect of flax genotypes (7 varieties), cultivation sites (two locations) and seasons (two years) were tested with a standard randomized complete block design, in search of a compromise for the production performance for both grain and straw, with the aim of reintroducing flax back into the northern Italian environment. Overall, grain yield reaches an average value of about 1.4 t ha−1 (dw), while straw yield reaches 2.77 t ha−1 (dw). The former is strictly dependent on the environmental effects of the growing site and season, while the effect of genotype was not significant. The straw yield also depends on the second-order interaction of the factors analyzed, although the performance of three varieties, Festival, Solal and Linoal, was noteworthy and seemed to respond well in both environments. Overall, it was found that flax can be conveniently grown for both grain and straw production. Full article
(This article belongs to the Topic Biomass for Energy, Chemicals and Materials)
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11 pages, 669 KiB  
Article
Incidence and Relative Survival of Patients with Merkel Cell Carcinoma in North Rhine-Westphalia, Germany, 2008–2021
by Andreas Stang, Lennart Möller, Ina Wellmann, Kevin Claaßen, Hiltraud Kajüter, Selma Ugurel and Jürgen C. Becker
Cancers 2024, 16(11), 2158; https://doi.org/10.3390/cancers16112158 (registering DOI) - 6 Jun 2024
Abstract
Background: To date, only a few population-representative studies have been carried out on the rare Merkel cell carcinoma (MCC). We provide incidence and survival estimates of MCC, including the conditional relative survival. Methods: We analyzed data from the cancer registry of North Rhine-Westphalia, [...] Read more.
Background: To date, only a few population-representative studies have been carried out on the rare Merkel cell carcinoma (MCC). We provide incidence and survival estimates of MCC, including the conditional relative survival. Methods: We analyzed data from the cancer registry of North Rhine-Westphalia, Germany, 2008–2021, covering a population of 18 million. We included all newly diagnosed MCCs and calculated age-standardized (old European Standard population) incidence rates and unconditional and conditional relative survival. Results: Our analysis included 2164 MCC patients. The age-standardized incidence of MCC was 5.2 (men) and 3.8 (women) per million person-years. The 5-year relative survival was 58.8% (men) and 70.7% (women). Survival was lower among men than women in all age–sex groups and was highest for MCC of the upper extremity in both men (68.2%) and women (79.3%). The sex difference in survival is particularly due to the better survival of women with MCC of the head and neck. In terms of survival, the first two years are particularly critical. Conclusions: Our data validate the worse survival among men and highlights a more favorable prognosis for MCCs located on the limbs. The first two years after diagnosis of MCC are the years with the highest excess mortality. Full article
(This article belongs to the Special Issue Skin Cancer: Risk Factors and Prevention)
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18 pages, 1772 KiB  
Article
Wastewater-Based Epidemiology for SARS-CoV-2 in Northern Italy: A Spatiotemporal Model
by Matilde Fondriest, Lorenzo Vaccari, Federico Aldrovandi, Laura De Lellis, Filippo Ferretti, Carmine Fiorentino, Erica Mari, Maria Grazia Mascolo, Laura Minelli, Vincenza Perlangeli, Giuseppe Bortone, Paolo Pandolfi, Annamaria Colacci and Andrea Ranzi
Int. J. Environ. Res. Public Health 2024, 21(6), 741; https://doi.org/10.3390/ijerph21060741 (registering DOI) - 6 Jun 2024
Abstract
The study investigated the application of Wastewater-Based Epidemiology (WBE) as a tool for monitoring the SARS-CoV-2 prevalence in a city in northern Italy from October 2021 to May 2023. Based on a previously used deterministic model, this study proposed a variation to account [...] Read more.
The study investigated the application of Wastewater-Based Epidemiology (WBE) as a tool for monitoring the SARS-CoV-2 prevalence in a city in northern Italy from October 2021 to May 2023. Based on a previously used deterministic model, this study proposed a variation to account for the population characteristics and virus biodegradation in the sewer network. The model calculated virus loads and corresponding COVID-19 cases over time in different areas of the city and was validated using healthcare data while considering viral mutations, vaccinations, and testing variability. The correlation between the predicted and reported cases was high across the three waves that occurred during the period considered, demonstrating the ability of the model to predict the relevant fluctuations in the number of cases. The population characteristics did not substantially influence the predicted and reported infection rates. Conversely, biodegradation significantly reduced the virus load reaching the wastewater treatment plant, resulting in a 30% reduction in the total virus load produced in the study area. This approach can be applied to compare the virus load values across cities with different population demographics and sewer network structures, improving the comparability of the WBE data for effective surveillance and intervention strategies. Full article
(This article belongs to the Topic Spatial Epidemiology and GeoInformatics)
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14 pages, 8408 KiB  
Article
Modified mRNA-Mediated CCN5 Gene Transfer Ameliorates Cardiac Dysfunction and Fibrosis without Adverse Structural Remodeling
by Min Ho Song, Jimeen Yoo, Do-A Kwon, Elena Chepurko, Sunghye Cho, Anthony Fargnoli, Roger J. Hajjar, Woo Jin Park, Lior Zangi and Dongtak Jeong
Int. J. Mol. Sci. 2024, 25(11), 6262; https://doi.org/10.3390/ijms25116262 (registering DOI) - 6 Jun 2024
Abstract
Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial [...] Read more.
Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA-CCN5 was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated CCN5 gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure. Full article
(This article belongs to the Special Issue Calcium Homeostasis of Cells in Health and Disease)
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18 pages, 5770 KiB  
Article
An Integrative Transcriptome Subtraction Strategy to Identify Human lncRNAs That Specifically Play a Role in Activation of Human Hepatic Stellate Cells
by Yonghe Ma, Jamie Harris, Ping Li, Chengfei Jiang, Hang Sun and Haiming Cao
Non-Coding RNA 2024, 10(3), 34; https://doi.org/10.3390/ncrna10030034 (registering DOI) - 6 Jun 2024
Abstract
Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from “activated” hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to [...] Read more.
Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from “activated” hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to define the role of human long non-coding RNAs (lncRNAs) in hHSC activation. To address this challenge, we identified another cell type that acts via a diverse gene network to promote fibrogenesis. Then, we identified the lncRNAs that were differentially regulated in activated hHSCs and the other profibrotic cell. Next, we conducted concurrent analysis to identify those lncRNAs that were specifically involved in fibrogenesis. We tested and confirmed that transdifferentiation of vascular smooth muscle cells (VSMCs) represents such a process. By overlapping TGFβ-regulated lncRNAs in multiple sets of hHSCs and VSMCs, we identified a highly selected list of lncRNA candidates that could specifically play a role in hHSC activation. We experimentally characterized one human lncRNA, named CARMN, which was significantly regulated by TGFβ in all conditions above. CARMN knockdown significantly reduced the expression levels of a panel of marker genes for hHSC activation, as well as the levels of ECM deposition and hHSC migration. Conversely, gain of function of CARMN using CRISPR activation (CRISPR-a) yielded the completely opposite effects. Taken together, our work addresses a bottleneck in identifying human lncRNAs that specifically play a role in hHSC activation and provides a framework to effectively select human lncRNAs with significant pathophysiological role. Full article
(This article belongs to the Special Issue Roles of Non-coding RNAs in Drug Metabolism and Disposition)
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12 pages, 209 KiB  
Article
Impact of Social Capital on Health Behaviors of Middle-Aged and Older Adults in China—An Analysis Based on CHARLS2020 Data
by Zheyu Wang, Yong Fang and Xingwei Zhang
Healthcare 2024, 12(11), 1154; https://doi.org/10.3390/healthcare12111154 (registering DOI) - 6 Jun 2024
Abstract
To actively respond to the challenges posed by population aging, people are paying more and more attention to healthy behavioral lifestyles, and the impact of social capital as an informal system on health behaviors cannot be ignored. This paper explores the impact of [...] Read more.
To actively respond to the challenges posed by population aging, people are paying more and more attention to healthy behavioral lifestyles, and the impact of social capital as an informal system on health behaviors cannot be ignored. This paper explores the impact of social capital on health behaviors of middle-aged and older adults based on 2020 CHARLS data. Using binary logistic regression models, we discussed the association between social capital and five health behaviors. The results suggest that structural social capital significantly increases physical activity and physical examination behaviors among middle-aged and older adults but also decreases the probability of abstinence behaviors. Cognitive social capital increases the probability that middle-aged and older adults will have a reasonable amount of sleep and physical activity. However, it also decreases the probability that smoking cessation behaviors will occur. Further attention needs to be paid to the role of social capital, the creation of a harmonious social environment and the enhancement of social trust, the strengthening of communities and grass-roots social organizations, and the provision of more platforms for the participation of middle-aged and older adults in social activities, to improve the quality of the healthy lives of middle-aged and older adults and, in turn, to promote the establishment of healthy behaviors. Full article
(This article belongs to the Special Issue Aging and Quality of Life)
20 pages, 22348 KiB  
Article
Genome-Wide Identification of NAC Transcription Factors in Chimonanthus praecox and Transgene CpNAC30 Affects Salt and Drought Tolerance in Arabidopsis
by Qing Yang, Yan Chen, Xiaohui Tang, Xueqi Zuo, Jing Li, Mingyang Li, Shunzhao Sui and Daofeng Liu
Horticulturae 2024, 10(6), 595; https://doi.org/10.3390/horticulturae10060595 (registering DOI) - 6 Jun 2024
Abstract
NAC (NAM, ATAF1/2, and CUC2) transcription factors regulate plant growth and development and response to various stresses. However, there is still limited insight into the NAC family in Chimonanthus praecox. This study performed a genome-wide characterization of the NAC transcription factor family [...] Read more.
NAC (NAM, ATAF1/2, and CUC2) transcription factors regulate plant growth and development and response to various stresses. However, there is still limited insight into the NAC family in Chimonanthus praecox. This study performed a genome-wide characterization of the NAC transcription factor family members in C. praecox. A total of 105 NAC family members were identified from the C. praecox genome. The phylogenetic tree categorized the CpNACs into nine groups and the accuracy of this classification was confirmed by the analysis results of conserved motifs, conserved domain, and gene structure. Cis-acting element analysis revealed that the promoters of CpNACs were abundant in elements responsive to various hormones and stresses, implying the functional diversity and complexity of CpNACs. Furthermore, we investigated the function of the CpNAC30. The expression level of CpNAC30 could be significantly induced by abiotic stress and the CpNAC30 was the highest expressed in mature leaves of C. praecox. Overexpression of CpNAC30 reduced salt stress tolerance of transgenic Arabidopsis. Nevertheless, the drought stress tolerance of transgenic plants was enhanced. This study lays a foundation for further understanding the function of CpNACs genes and provides insights for abiotic stress tolerance breeding of C. praecox and other woody plants. Full article
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19 pages, 5424 KiB  
Systematic Review
Network Structure of Online Customer Reviews and Online Hotel Reviews: A Systematic Literature Review
by Maria Helena Pestana, Manuel Gageiro, José António C. Santos and Margarida Custódio Santos
Information 2024, 15(6), 334; https://doi.org/10.3390/info15060334 (registering DOI) - 6 Jun 2024
Abstract
This study conducts a bibliometric analysis of online customer and hotel review research, aiming to provide insights into where each field comes from, stands now and ought to go in the future. In particular, this study examines how the existing research on online [...] Read more.
This study conducts a bibliometric analysis of online customer and hotel review research, aiming to provide insights into where each field comes from, stands now and ought to go in the future. In particular, this study examines how the existing research on online customer reviews can benefit future hotel review research. Data collected from Web-of-Science and Scopus created an expanded network of 797 core articles and 19,374 citations to identify intellectual structures, developing trends, and future research gaps. This study offers a visual overview of journals, institutions, countries, research themes and authors to assess the overall directions hotels can take. It underscores the necessity for rigorous and relevant research amid the proliferation of online reviews and emphasises the imperative for academia to bridge the gap between theoretical insights and practical applications within the dynamic tourism industry. This study provides researchers and industry professionals with useful tools to understand and deal with the complexities of online reviews. It also highlights the important role these reviews play in shaping the future of tourism strategies. Full article
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12 pages, 1866 KiB  
Article
Urinary Hydroxyproline as an Inflammation-Independent Biomarker of Inflammatory Bowel Disease
by Muriel Huss, Tanja Elger, Johanna Loibl, Arne Kandulski, Benedicta Binder, Petra Stoeckert, Patricia Mester, Martina Müller, Christa Buechler and Hauke Christian Tews
Gastroenterol. Insights 2024, 15(2), 486-497; https://doi.org/10.3390/gastroent15020035 (registering DOI) - 6 Jun 2024
Abstract
Predicting responses and monitoring the severity of inflammatory bowel disease (IBD) is challenging due to a lack of specific biomarkers. This study identifies urinary hydroxyproline, a marker of collagen turnover elevated in experimental colitis, as independent of conventional biomarkers like creatinine, glomerular filtration [...] Read more.
Predicting responses and monitoring the severity of inflammatory bowel disease (IBD) is challenging due to a lack of specific biomarkers. This study identifies urinary hydroxyproline, a marker of collagen turnover elevated in experimental colitis, as independent of conventional biomarkers like creatinine, glomerular filtration rate, C-reactive protein, and fecal calprotectin. Among 71 IBD patients, urinary hydroxyproline levels were significantly higher compared with 36 controls, with an area under the receiver operating characteristic curve of 0.814, highlighting its potential as a diagnostic tool. No significant difference in hydroxyproline levels was observed between the 50 Crohn’s disease and 21 ulcerative colitis patients, nor was there a correlation with kidney function markers, gastrointestinal symptom severity, or stool consistency. Disease localization was not associated with urinary hydroxyproline levels. Interestingly, 14 patients with primary sclerosing cholangitis and IBD also exhibited elevated urinary hydroxyproline levels, comparable to IBD patients but higher than healthy controls. This underscores the role of urinary hydroxyproline as an independent biomarker for IBD diagnosis, without association with disease severity or established markers like fecal calprotectin. Full article
(This article belongs to the Section Gastrointestinal Disease)
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15 pages, 771 KiB  
Review
Generalized Pustular Psoriasis and Systemic Organ Dysfunctions
by Romane Teshima, Natsuko Saito-Sasaki and Yu Sawada
Int. J. Mol. Sci. 2024, 25(11), 6270; https://doi.org/10.3390/ijms25116270 (registering DOI) - 6 Jun 2024
Abstract
This review explores the intricate relationship between generalized pustular psoriasis (GPP) and various systemic diseases, shedding light on the broader impacts of this severe skin condition beyond its primary dermatological manifestations. GPP is identified as not only a profound contributor to skin pathology [...] Read more.
This review explores the intricate relationship between generalized pustular psoriasis (GPP) and various systemic diseases, shedding light on the broader impacts of this severe skin condition beyond its primary dermatological manifestations. GPP is identified as not only a profound contributor to skin pathology but also a significant risk factor for systemic diseases affecting cardiovascular, hepatic, renal, pulmonary, and skeletal systems, as well as associated with an increased incidence of anemia, depression, anxiety, and arthritis. The research highlights the complex interplay of cytokines, particularly IL-17 and IL-36, which are central to the pathophysiology of GPP and implicated in the exacerbation of systemic conditions. Key findings indicate a higher incidence of cardiovascular events in GPP patients compared to those with other severe forms of psoriasis, notably with a stronger correlation between myocardial infarction history and GPP development. Liver disturbances, frequently reversible upon psoriasis remission, suggest a cytokine-mediated link to hepatic health. Renal dysfunction appears elevated in GPP sufferers, with IL-17 and IL-36 potentially driving renal fibrosis. Similarly, interstitial lung disease and osteoporosis in GPP patients underscore the systemic reach of inflammatory processes initiated in the skin. The associations with anemia, depression, anxiety, and arthritis further complicate the clinical management of GPP, requiring a multidisciplinary approach. The study concludes that managing GPP effectively requires a holistic approach that addresses both the cutaneous and systemic dimensions of the disease, advocating for continued research into the mechanisms that connect GPP with broader health implications to refine therapeutic strategies. Full article
(This article belongs to the Section Molecular Biology)
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18 pages, 2531 KiB  
Review
The State-of-the-Art Antibacterial Activities of Glycyrrhizin: A Comprehensive Review
by Ru-Yi Chen, Jin-Jin Shi, Yan-Jun Liu, Jing Yu, Chang-Yun Li, Fan Tao, Jia-Feng Cao, Guan-Jun Yang and Jiong Chen
Microorganisms 2024, 12(6), 1155; https://doi.org/10.3390/microorganisms12061155 (registering DOI) - 6 Jun 2024
Abstract
Licorice (Glycyrrhiza glabra) is a plant of the genus Glycyrrhiza in the family Fabaceae/Leguminosae and is a renowned natural herb with a long history of medicinal use dating back to ancient times. Glycyrrhizin (GLY), the main active component of [...] Read more.
Licorice (Glycyrrhiza glabra) is a plant of the genus Glycyrrhiza in the family Fabaceae/Leguminosae and is a renowned natural herb with a long history of medicinal use dating back to ancient times. Glycyrrhizin (GLY), the main active component of licorice, serves as a widely utilized therapeutic agent in clinical practice. GLY exhibits diverse medicinal properties, including anti-inflammatory, antibacterial, antiviral, antitumor, immunomodulatory, intestinal environment maintenance, and liver protection effects. However, current research primarily emphasizes GLY’s antiviral activity, while providing limited insight into its antibacterial properties. GLY demonstrates a broad spectrum of antibacterial activity via inhibiting the growth of bacteria by targeting bacterial enzymes, impacting cell membrane formation, and altering membrane permeability. Moreover, GLY can also bolster host immunity by activating pertinent immune pathways, thereby enhancing pathogen clearance. This paper reviews GLY’s inhibitory mechanisms against various pathogenic bacteria-induced pathological changes, its role as a high-mobility group box 1 inhibitor in immune regulation, and its efficacy in combating diseases caused by pathogenic bacteria. Furthermore, combining GLY with other antibiotics reduces the minimum inhibitory concentration, potentially aiding in the clinical development of combination therapies against drug-resistant bacteria. Sources of information were searched using PubMed, Web of Science, Science Direct, and GreenMedical for the keywords “licorice”, “Glycyrrhizin”, “antibacterial”, “anti-inflammatory”, “HMGB1”, and combinations thereof, mainly from articles published from 1979 to 2024, with no language restrictions. Screening was carried out by one author and supplemented by others. Papers with experimental flaws in their experimental design and papers that did not meet expectations (antifungal papers, etc.) were excluded. Full article
(This article belongs to the Special Issue Research on Natural Products against Pathogens)
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29 pages, 1547 KiB  
Systematic Review
Systematic Literature Review of Land Use Conflicts in Northern Sweden—Lessons Learned and Ways Forward
by Jerbelle Elomina and Ivana Živojinović
Resources 2024, 13(6), 77; https://doi.org/10.3390/resources13060077 (registering DOI) - 6 Jun 2024
Abstract
Land use conflicts are intensifying in Northern Sweden due to the increasing global demand for resources coupled with the green transition. In line with this, a thorough understanding of land use conflicts in the area is becoming necessary as economic activities expand and [...] Read more.
Land use conflicts are intensifying in Northern Sweden due to the increasing global demand for resources coupled with the green transition. In line with this, a thorough understanding of land use conflicts in the area is becoming necessary as economic activities expand and newer ones are developed. Hence, this paper aims to provide a systematic literature review of research on land use conflicts specific to Northern Sweden, focusing on various economic activities such as forestry, mining, tourism, energy sector and reindeer husbandry. Additionally, we aim to determine lessons learned and suggested ways forward based on a systematic review. We used Scopus and Web of Science on June 2023 and through descriptive statistical analysis of 33 articles, we summarized research trends and gaps. We found three main typologies of conflicts and five main themes of suggested ways forward. Recommendations agree that there should be a broader understanding of the underlying interests of the stakeholders; and there should be an inclusive, more participatory approach to discussing potential solutions, not to create an agreement but to come to an understanding. Beyond academic insights, the findings hold practical relevance for shaping effective land use policies. This paper offers valuable lessons that extend beyond the local context, informing broader discussions and policy considerations for sustainable land management in the larger Arctic setting, where similar challenges and resource demands are unfolding. Full article
(This article belongs to the Special Issue Minerals and Land-Use Planning: Sustainable Narratives and Practices)
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