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Article
Can the Carbon Emissions Trading System Improve the Green Total Factor Productivity of the Pilot Cities?—A Spatial Difference-in-Difference Econometric Analysis in China
Int. J. Environ. Res. Public Health 2022, 19(3), 1209; https://doi.org/10.3390/ijerph19031209 (registering DOI) - 22 Jan 2022
Abstract
The carbon emission trading system (CETS) is an important market-oriented policy tool for the Chinese government to solve the problem of high emissions and achieve the growth of green total factor productivity (GTFP). This study makes up for the neglect of the spatial [...] Read more.
The carbon emission trading system (CETS) is an important market-oriented policy tool for the Chinese government to solve the problem of high emissions and achieve the growth of green total factor productivity (GTFP). This study makes up for the neglect of the spatial effect of CETS policy in previous studies and adopts the spatial difference-in-differences (DID) Durbin model (SDID-SDM) method of two-way fixed effects to scientifically identify the direct and spatial effects influencing the mechanisms and heterogeneity of CETS on urban GTFP based on the panel data of 281 cities in China from 2004 to 2017. It found that China’s CETS significantly improved the GTFP of pilot cities but produced a negative spatial siphon effect that restricted the growth of GTFP in surrounding cities. Benchmark results are robust under the placebo test, the propensity score matching SDID (PSM-SDID) test, and the difference-in difference-in-differences (DDD) test. The mechanism analysis shows that the CETS effect is mainly realized by improving energy efficiency, promoting low-carbon innovation, adjusting the industrial structure, and enhancing financial agglomeration. In addition, we find that policy effects are better in cities with high marketization, strong monitoring reporting and verification (MRV) capabilities, high coal endowment, and high financial endowment. Overall, China’s CETS policy achieves the goal of enhancing GTFP but needs to pay attention to the spatial siphon effect. In addition, our estimation strategy can serve as a scientific reference for similar studies in other developing countries. Full article
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Article
Solar Heterogenous Photocatalytic Degradation of Methylthionine Chloride on a Flat Plate Reactor: Effect of pH and H2O2 Addition
Catalysts 2022, 12(2), 132; https://doi.org/10.3390/catal12020132 (registering DOI) - 21 Jan 2022
Abstract
Methylthionine chloride (MTC) is a compound with several applications both in the clinical and medical industries. Nevertheless, such compounds can become an environmental problem, as they are not properly treated by wastewater treatment plants. This objective of this work was to study MTC [...] Read more.
Methylthionine chloride (MTC) is a compound with several applications both in the clinical and medical industries. Nevertheless, such compounds can become an environmental problem, as they are not properly treated by wastewater treatment plants. This objective of this work was to study MTC degradation in a flat plate reactor through solar photolysis and heterogeneous photocatalysis processes with TiO2 as a catalyst. In addition to the processes, three pH (3.5, 6.5, and 9) and the effect of H2O2 addition (no dose, 0.5, and 1 mM/L) were tested. The results show that acidic pH is the most appropriate for MTC degradation, which ranged between 56% and 68.7% for photolysis and between 76% and 86.7% in photocatalysis. The H2O2 addition resulted in lower degradation in all cases, leading the authors to conclude that the presence of peroxide actually hinders degradation in solar photolysis and photocatalysis processes. Statistical analysis showed that the constant rate reactions calculated for every process, under the same conditions of pH and H2O2 addition, are significantly different from one another, and the three factors considered for experimental design (process, pH, and H2O2) have a statistically significant effect on MTC degradation. The collector area per order confirmed higher efficiency for photocatalysis when compared to photolysis processes. Full article
(This article belongs to the Special Issue Catalysis for the Removal of Water Pollutants)
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Article
Poly-Lysine Dendritic Nanocarrier to Target Epidermal Growth Factor Receptor Overexpressed Breast Cancer for Methotrexate Delivery
Materials 2022, 15(3), 800; https://doi.org/10.3390/ma15030800 - 21 Jan 2022
Abstract
A fourth generation poly-lysine dendritic nanocarrier (P4LDN)-based targeted chemotherapy for breast cancer is attempted by incorporating an epidermal growth factor receptor (EGFR)-specific short peptide E2 (ARSHVGYTGAR) and the drug methotrexate (MTX) into a nanocarrier system. The drug is incorporated into the [...] Read more.
A fourth generation poly-lysine dendritic nanocarrier (P4LDN)-based targeted chemotherapy for breast cancer is attempted by incorporating an epidermal growth factor receptor (EGFR)-specific short peptide E2 (ARSHVGYTGAR) and the drug methotrexate (MTX) into a nanocarrier system. The drug is incorporated into the nanocarrier using a cathepsin B cleavable spacer: glycine–phenylalanine–leucine–glycine (GFLG). The in vitro analysis of the time-dependent drug release, binding and internalization ability, and the cytotoxic nature showed that this drug delivery system (DDS) is highly effective. The efficacy analysis using non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice also showed that compared to the control group, the DDS can effectively reduce tumor volume. The mice that received the DDS appeared to gain weight more rapidly than the free drug, which suggests that the dendrimer is more easily tolerated by mice than the free drug. Full article
(This article belongs to the Special Issue Targeted Drug Delivery)
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Review
Angioprevention of Urologic Cancers by Plant-Derived Foods
Pharmaceutics 2022, 14(2), 256; https://doi.org/10.3390/pharmaceutics14020256 (registering DOI) - 21 Jan 2022
Abstract
The number of cancer cases worldwide keeps growing unstoppably, despite the undeniable advances achieved by basic research and clinical practice. Urologic tumors, including some as prevalent as prostate, bladder or kidney tumors, are no exceptions to this rule. Moreover, the fact that many [...] Read more.
The number of cancer cases worldwide keeps growing unstoppably, despite the undeniable advances achieved by basic research and clinical practice. Urologic tumors, including some as prevalent as prostate, bladder or kidney tumors, are no exceptions to this rule. Moreover, the fact that many of these tumors are detected in early stages lengthens the duration of their treatment, with a significant increase in health care costs. In this scenario, prevention offers the most cost-effective long-term strategy for the global control of these diseases. Although specialized diets are not the only way to decrease the chances to develop cancer, epidemiological evidence support the role of certain plant-derived foods in the prevention of urologic cancer. In many cases, these plants are rich in antiangiogenic phytochemicals, which could be responsible for their protective or angiopreventive properties. Angiogenesis inhibition may contribute to slow down the progression of the tumor at very different stages and, for this reason, angiopreventive strategies could be implemented at different levels of chemoprevention, depending on the targeted population. In this review, epidemiological evidence supporting the role of certain plant-derived foods in urologic cancer prevention are presented, with particular emphasis on their content in bioactive phytochemicals that could be used in the angioprevention of cancer. Full article
(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies)
Article
Platelet Count and Survival after Cancer
Cancers 2022, 14(3), 549; https://doi.org/10.3390/cancers14030549 (registering DOI) - 21 Jan 2022
Abstract
Thrombocytosis is associated with cancer progression and death for many cancer types. It is unclear if platelet count is also associated with cancer survival. We conducted a cohort study of 112,231 adults in Ontario with a diagnosis of cancer between January 2007 and [...] Read more.
Thrombocytosis is associated with cancer progression and death for many cancer types. It is unclear if platelet count is also associated with cancer survival. We conducted a cohort study of 112,231 adults in Ontario with a diagnosis of cancer between January 2007 and December 2016. We included patients who had a complete blood count (CBC) completed in the 30 days prior to their cancer diagnosis. Subjects were assigned to one of three categories according to platelet count: low (≤25th percentile), medium (>25 to <75th percentile), and high (≥75th percentile). Study subjects were followed from the date of their cancer diagnosis for cancer-specific death. Of the 112,231 eligible cancer patients in the cohort study, 40,329 (35.9%) died from their cancer in the follow-up period. Relative to those with a medium platelet count, the rate of cancer-specific death was higher among individuals with a high platelet count (HR 1.52; 95%CI 1.48–1.55) and was lower among individuals with a low platelet count (HR 0.91; 95%CI 0.88–0.93). A high platelet count was associated with poor survival for many cancer types. Platelet count could potentially be used as a risk stratification measure for cancer patients. Full article
Review
Endocrine Disruptors and Prostate Cancer
Int. J. Mol. Sci. 2022, 23(3), 1216; https://doi.org/10.3390/ijms23031216 (registering DOI) - 21 Jan 2022
Abstract
The role of endocrine disruptors (EDs) in the human prostate gland is an overlooked issue even though the prostate is essential for male fertility. From experimental models, it is known that EDs can influence several molecular mechanisms involved in prostate homeostasis and diseases, [...] Read more.
The role of endocrine disruptors (EDs) in the human prostate gland is an overlooked issue even though the prostate is essential for male fertility. From experimental models, it is known that EDs can influence several molecular mechanisms involved in prostate homeostasis and diseases, including prostate cancer (PCa), one of the most common cancers in the male, whose onset and progression is characterized by the deregulation of several cellular pathways including androgen receptor (AR) signaling. The prostate gland essentiality relies on its function to produce and secrete the prostatic fluid, a component of the seminal fluid, needed to keep alive and functional sperms upon ejaculation. In physiological condition, in the prostate epithelium the more-active androgen, the 5α-dihydrotestosterone (DHT), formed from testosterone (T) by the 5α-reductase enzyme (SRD5A), binds to AR and, upon homodimerization and nuclear translocation, recognizes the promoter of target genes modulating them. In pathological conditions, AR mutations and/or less specific AR binding by ligands modulate differently targeted genes leading to an altered regulation of cell proliferation and triggering PCa onset and development. EDs acting on the AR-dependent signaling within the prostate gland can contribute to the PCa onset and to exacerbating its development. Full article
(This article belongs to the Special Issue Advances in Endocrine Disruptors)
Brief Report
Functional Innovation through Gene Duplication Followed by Frameshift Mutation
Genes 2022, 13(2), 190; https://doi.org/10.3390/genes13020190 (registering DOI) - 21 Jan 2022
Abstract
In his influential book “Evolution by Gene Duplication”, Ohno postulated that frameshift mutation could lead to a new function after duplication, but frameshift mutation is generally thought to be deleterious, and thus drew little attention in functional innovation in duplicate evolution. [...] Read more.
In his influential book “Evolution by Gene Duplication”, Ohno postulated that frameshift mutation could lead to a new function after duplication, but frameshift mutation is generally thought to be deleterious, and thus drew little attention in functional innovation in duplicate evolution. To this end, we here report an exhaustive survey of the genomes of human, mouse, zebrafish, and fruit fly. We identified 80 duplicate genes that involved frameshift mutations after duplication. The frameshift mutation preferentially located close to the C-terminus in most cases (55/88), which indicated that a frameshift mutation that changed the reading frame in a small part at the end of a duplicate may likely have contributed to adaptive evolution (e.g., human genes NOTCH2NL and ARHGAP11B) otherwise too deleterious to survive. A few cases (11/80) involved multiple frameshift mutations, exhibiting various patterns of modifications of the reading frame. Functionality of duplicate genes involving frameshift mutations was confirmed by sequence characteristics and expression profile, suggesting a potential role of frameshift mutation in creating functional novelty. We thus showed that genomes have non-negligible numbers of genes that have experienced frameshift mutations following gene duplication. Our results demonstrated the potential importance of frameshift mutations in molecular evolution, as Ohno verbally argued 50 years ago. Full article
(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)
Article
Novel NK1R-Targeted 68Ga-/177Lu-Radioconjugates with Potential Application against Glioblastoma Multiforme: Preliminary Exploration of Structure–Activity Relationships
Int. J. Mol. Sci. 2022, 23(3), 1214; https://doi.org/10.3390/ijms23031214 (registering DOI) - 21 Jan 2022
Abstract
Locoregionally administered, NK1 receptor (NK1R) targeted radionuclide therapy is a promising strategy for the treatment of glioblastoma multiforme. So far, the radiopharmaceuticals used in this approach have been based on the endogenous agonist of NK1R, Substance P or on its close analogues. Herein, [...] Read more.
Locoregionally administered, NK1 receptor (NK1R) targeted radionuclide therapy is a promising strategy for the treatment of glioblastoma multiforme. So far, the radiopharmaceuticals used in this approach have been based on the endogenous agonist of NK1R, Substance P or on its close analogues. Herein, we used a well-known, small molecular NK1R antagonist, L732,138, as the basis for the radiopharmaceutical vector. First, 14 analogues of this compound were evaluated to check whether extending the parent structure with linkers of different lengths would not deteriorate the NK1R binding. The tested analogues had affinity similar to or better than the parent compound, and none of the linkers had a negative impact on the binding. Next, five DOTA conjugates were synthesized and used for labelling with 68Ga and 177Lu. The obtained radioconjugates turned out to be fairly lipophilic but showed rather limited stability in human plasma. Evaluation of the receptor affinity of the (radio)conjugates showed that neither the chelator nor the metal negatively impacts the NK1R binding. The 177Lu-radioconjugates exhibited the binding characteristics towards NK1R similar or better than that of the 177Lu-labelled derivative of Substance P, which is in current clinical use. The experimental results presented herein, along with their structural rationalization provided by modelling, give insight for the further molecular design of small molecular NK1R-targeting vectors. Full article
(This article belongs to the Special Issue Glioblastoma 2.0)
Review
Metabolomic Fingerprinting for the Detection of Early-Stage Lung Cancer: From the Genome to the Metabolome
Int. J. Mol. Sci. 2022, 23(3), 1215; https://doi.org/10.3390/ijms23031215 (registering DOI) - 21 Jan 2022
Abstract
The five-year survival rate of lung cancer patients is very low, mainly because most newly diagnosed patients present with locally advanced or metastatic disease. Therefore, early diagnosis is key to the successful treatment and management of lung cancer. Unfortunately, early detection methods of [...] Read more.
The five-year survival rate of lung cancer patients is very low, mainly because most newly diagnosed patients present with locally advanced or metastatic disease. Therefore, early diagnosis is key to the successful treatment and management of lung cancer. Unfortunately, early detection methods of lung cancer are not ideal. In this brief review, we described early detection methods such as chest X-rays followed by bronchoscopy, sputum analysis followed by cytological analysis, and low-dose computed tomography (LDCT). In addition, we discussed the potential of metabolomic fingerprinting, compared to that of other biomarkers, including molecular targets, as a low-cost, high-throughput blood-based test that is both feasible and affordable for early-stage lung cancer screening of at-risk populations. Accordingly, we proposed a paradigm shift to metabolomics as an alternative to molecular and proteomic-based markers in lung cancer screening, which will enable blood-based routine testing and be accessible to those patients at the highest risk for lung cancer. Full article
(This article belongs to the Special Issue Biomarkers for Early Detection of Cancer: Molecular Aspects)
Article
Investigating the Potential of Isolating and Expanding Tumour-Infiltrating Lymphocytes from Adult Sarcoma
Cancers 2022, 14(3), 548; https://doi.org/10.3390/cancers14030548 (registering DOI) - 21 Jan 2022
Abstract
Sarcomas are a heterogeneous group of mesenchymal neoplasms, many of which are associated with a high risk of metastasis and poor prognosis. Conventional chemotherapy and targeted therapies have varying effects across individuals and tumour subtypes. The current therapies frequently provide limited clinical benefit; [...] Read more.
Sarcomas are a heterogeneous group of mesenchymal neoplasms, many of which are associated with a high risk of metastasis and poor prognosis. Conventional chemotherapy and targeted therapies have varying effects across individuals and tumour subtypes. The current therapies frequently provide limited clinical benefit; hence, more effective treatments are urgently needed. Recent advances in immunotherapy, such as checkpoint inhibition or adoptive cell therapy (ACT), show potential in increasing efficacy by providing a more personalized treatment. Therapy with tumour-infiltrating lymphocytes (TILs) is an emerging field in immunotherapy. Here, we collected 190 sarcoma tumour specimens from patients without pre­operative adjuvant treatment in order to isolate TILs. We compared different methods of TIL expansion and optimized a protocol specifically for efficacy in culturing TILs from sarcoma. The expanded TIL populations were characterized by flow cytometry analysis using CD3, CD4, CD8, CD14, CD19 and CD56 markers. The TIL populations were non­specifically stimulated to establish TIL reactivity. Through an optimized expansion protocol, TILs were isolated and cultured from 54 of 92 primary sarcoma specimens. The isolated TILs varied in CD4+ and CD8+ T-cell compositions and retained their ability to release IFNγ upon stimulation. Our results suggest that certain sarcoma subtypes have the potential to yield a sufficient number of TILs for TIL therapy. Full article
(This article belongs to the Special Issue Targeted Treatment for Soft Tissue Sarcoma and Bone Sarcoma)
Article
Resveratrol Treatment Prevents Increase of Mast Cells in Both Murine OVA Enteritis and IL-10−/− Colitis
Int. J. Mol. Sci. 2022, 23(3), 1213; https://doi.org/10.3390/ijms23031213 (registering DOI) - 21 Jan 2022
Abstract
Mast cells are involved in allergic and other inflammatory diseases. The polyphenol resveratrol is known for its anti-inflammatory properties and may be used as nutraceutical in mast cell associated diseases. We analyzed the effect of resveratrol on mast cells in vivo in ovalbumin-induced [...] Read more.
Mast cells are involved in allergic and other inflammatory diseases. The polyphenol resveratrol is known for its anti-inflammatory properties and may be used as nutraceutical in mast cell associated diseases. We analyzed the effect of resveratrol on mast cells in vivo in ovalbumin-induced allergic enteritis as well as experimental colitis in IL-10−/− mice which received resveratrol via drinking water. Treatment with resveratrol prevented the increase in mast cells in both allergic enteritis and chronic colitis in duodenum as well as in colon. Further, it delayed the onset of diseases symptoms and ameliorated diseases associated parameters such as tissue damage as well as inflammatory cell infiltration in affected colon sections. In addition to the findings in vivo, resveratrol inhibited IgE-dependent degranulation and expression of pro-inflammatory cytokines such as TNF-α in IgE/DNP-activated as well as in LPS-activated bone marrow-derived mast cells. These results indicate that resveratrol may be considered as an anti-allergic and anti-inflammatory plant-derived component for the prevention or treatment of mast cell-associated disorders of the gastrointestinal tract. Full article
Review
Selected Natural Products in Neuroprotective Strategies for Alzheimer’s Disease-A Non-Systematic Review
Int. J. Mol. Sci. 2022, 23(3), 1212; https://doi.org/10.3390/ijms23031212 (registering DOI) - 21 Jan 2022
Abstract
Neurodegenerative disorders such as Alzheimer’s disease (AD) are distinguished by the irreversible degeneration of central nervous system function and structure. AD is characterized by several different neuropathologies—among others, it interferes with neuropsychiatrical controls and cognitive functions. This disease is the number one neurodegenerative [...] Read more.
Neurodegenerative disorders such as Alzheimer’s disease (AD) are distinguished by the irreversible degeneration of central nervous system function and structure. AD is characterized by several different neuropathologies—among others, it interferes with neuropsychiatrical controls and cognitive functions. This disease is the number one neurodegenerative disorder; however, its treatment options are few and, unfortunately, ineffective. In the new strategies devised for AD prevention and treatment, the application of plant-based natural products is especially popular due to lesser side effects associated with their taking. Moreover, their neuroprotective activities target different pathological mechanisms. The current review presents the anti-AD properties of several natural plant substances. The paper throws light on products under in vitro and in vivo trials and compiles information on their mechanism of actions. Knowledge of the properties of such plant compounds and their combinations will surely lead to discovering new potent medicines for the treatment of AD with lesser side effects than the currently available pharmacological proceedings. Full article
Review
p27, The Cell Cycle and Alzheimer´s Disease
Int. J. Mol. Sci. 2022, 23(3), 1211; https://doi.org/10.3390/ijms23031211 (registering DOI) - 21 Jan 2022
Abstract
The cell cycle consists of successive events that lead to the generation of new cells. The cell cycle is regulated by different cyclins, cyclin-dependent kinases (CDKs) and their inhibitors, such as p27Kip1. At the nuclear level, p27Kip1 has the ability [...] Read more.
The cell cycle consists of successive events that lead to the generation of new cells. The cell cycle is regulated by different cyclins, cyclin-dependent kinases (CDKs) and their inhibitors, such as p27Kip1. At the nuclear level, p27Kip1 has the ability to control the evolution of different phases of the cell cycle and oppose cell cycle progression by binding to CDKs. In the cytoplasm, diverse functions have been described for p27Kip1, including microtubule remodeling, axonal transport and phagocytosis. In Alzheimer’s disease (AD), alterations to cycle events and a purported increase in neurogenesis have been described in the early disease process before significant pathological changes could be detected. However, most neurons cannot progress to complete their cell division and undergo apoptotic cell death. Increased levels of both the p27Kip1 levels and phosphorylation status have been described in AD. Increased levels of Ab42, tau hyperphosphorylation or even altered insulin signals could lead to alterations in p27Kip1 post-transcriptional modifications, causing a disbalance between the levels and functions of p27Kip1 in the cytoplasm and nucleus, thus inducing an aberrant cell cycle re-entry and alteration of extra cell cycle functions. Further studies are needed to completely understand the role of p27Kip1 in AD and the therapeutic opportunities associated with the modulation of this target. Full article
Article
Potential Owner-Related Risk Factors That May Contribute to Obesity in Companion Dogs in Aotearoa New Zealand
Animals 2022, 12(3), 267; https://doi.org/10.3390/ani12030267 (registering DOI) - 21 Jan 2022
Abstract
Approximately a third of all Aotearoa New Zealand (NZ) households include a dog, with 28% of these dogs being overweight or obese, conditions that are associated with many serious health issues. Therefore, healthy weight interventions that focus on the owner’s role are of [...] Read more.
Approximately a third of all Aotearoa New Zealand (NZ) households include a dog, with 28% of these dogs being overweight or obese, conditions that are associated with many serious health issues. Therefore, healthy weight interventions that focus on the owner’s role are of great importance to companion animal welfare in NZ. Accordingly, the present study explores the feeding practices associated with NZ dogs and identifies potential owner-related risk factors contributing to these animals being overweight or obese. The current study used data collected from a survey conducted online in 2019 between January and March of NZ residents over 18. Along with demographic questions, the respondents were asked questions regarding their dog’s body condition and diet questions related to the body. Nearly a quarter (26%, n = 609) of the survey participants (n = 2358) owned at least one dog. The current study reported that increasing age range, household income and the number of children increased the likelihood of having a dog while increasing qualification level and living in a town/city decreased the likelihood. The majority of the respondents fed their dog(s) treats (59%) and 85% fed them specialised food bought from a pet shop, veterinary clinic and/or different online sources. Just over a third of the participant (39%) reported that they fed their dog(s) biscuits from the supermarket, 36% fed their dog(s) raw meat, and 34% of respondents fee their dog(s) table scraps/human food. These results suggest that many dog owners feed their dog(s) various food types, making it a challenging task to determine the exact amount required from each type in order not to exceed caloric intake. Disagreement regarding the correct body condition were reported among twenty per cent of the respondents. This finding indicates a knowledge gap among the NZ dog-owning population that may negatively affect their dogs’ welfare and wellbeing. Future research into pro-equity approaches to address these issues is needed so that dogs in NZ can live not only a good life but also their best life. Full article
(This article belongs to the Special Issue Animal Nutrition for Small Animal Health)
Article
THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors
Int. J. Mol. Sci. 2022, 23(3), 1207; https://doi.org/10.3390/ijms23031207 (registering DOI) - 21 Jan 2022
Abstract
Multiple myeloma (MM) is a hematological disease marked by abnormal growth of B cells in bone marrow. Inherent chromosomal instability and DNA damage are major hallmarks of MM, which implicates an aberrant DNA repair mechanism. Studies have implicated a role for CDK12 in [...] Read more.
Multiple myeloma (MM) is a hematological disease marked by abnormal growth of B cells in bone marrow. Inherent chromosomal instability and DNA damage are major hallmarks of MM, which implicates an aberrant DNA repair mechanism. Studies have implicated a role for CDK12 in the control of expression of DNA damage response genes. In this study, we examined the effect of a small molecule inhibitor of CDK12–THZ531 on MM cells. Treatment of MM cells with THZ531 led to heightened cell death accompanied by an extensive effect on gene expression changes. In particular, we observed downregulation of genes involved in DNA repair pathways. With this insight, we extended our study to identify synthetic lethal mechanisms that could be exploited for the treatment of MM cells. Combination of THZ531 with either DNA-PK inhibitor (KU-0060648) or PARP inhibitor (Olaparib) led to synergistic cell death. In addition, combination treatment of THZ531 with Olaparib significantly reduced tumor burden in animal models. Our findings suggest that using a CDK12 inhibitor in combination with other DNA repair inhibitors may establish an effective therapeutic regimen to benefit myeloma patients. Full article
(This article belongs to the Section Biochemistry)
Article
The Effect of High Protein Powder Structure on Hydration, Glass Transition, Water Sorption, and Thermomechanical Properties
Foods 2022, 11(3), 292; https://doi.org/10.3390/foods11030292 (registering DOI) - 21 Jan 2022
Abstract
Poor solubility of high protein milk powders can be an issue during the production of nutritional formulations, as well as for end-users. One possible way to improve powder solubility is through the creation of vacuoles and pores in the particle structure using high [...] Read more.
Poor solubility of high protein milk powders can be an issue during the production of nutritional formulations, as well as for end-users. One possible way to improve powder solubility is through the creation of vacuoles and pores in the particle structure using high pressure gas injection during spray drying. The aim of this study was to determine whether changes in particle morphology effect physical properties, such as hydration, water sorption, structural strength, glass transition temperature, and α-relaxation temperatures. Four milk protein concentrate powders (MPC, 80%, w/w, protein) were produced, i.e., regular (R) and agglomerated (A) without nitrogen injection and regular (RN) and agglomerated (AN) with nitrogen injection. Electron microscopy confirmed that nitrogen injection increased powder particles’ sphericity and created fractured structures with pores in both regular and agglomerated systems. Environmental scanning electron microscopy (ESEM) showed that nitrogen injection enhanced the moisture uptake and solubility properties of RN and AN as compared with non-nitrogen-injected powders (R and A). ). In particular, at the final swelling at over 100% relative humidity (RH), R, A, AN, and RN powders showed an increase in particle size of 25, 20, 40, and 97% respectively. The injection of nitrogen gas (NI) did not influence calorimetric glass transition temperature (Tg), which could be expected as there was no change to the powder composition, however, the agglomeration of powders did effect Tg. Interestingly, the creation of porous powder particles by NI did alter the α-relaxation temperatures (up to ~16 °C difference between R and AN powders at 44% RH) and the structural strength (up to ~11 °C difference between R and AN powders at 44% RH). The results of this study provide an in-depth understanding of the changes in the morphology and physical-mechanical properties of nitrogen gas-injected MPC powders. Full article
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Article
Molecular Modelling of Optical Biosensor Phosphorene-Thioguanine for Optimal Drug Delivery in Leukemia Treatment
Cancers 2022, 14(3), 545; https://doi.org/10.3390/cancers14030545 (registering DOI) - 21 Jan 2022
Abstract
Thioguanine is an anti-cancer drug used for the treatment of leukemia. However, thioguanine has weak aqueous solubility and low biocompatibility, which limits its performance in the treatment of cancer. In the present work, these inadequacies were targeted using density functional theory-based simulations. Three stable configurations were [...] Read more.
Thioguanine is an anti-cancer drug used for the treatment of leukemia. However, thioguanine has weak aqueous solubility and low biocompatibility, which limits its performance in the treatment of cancer. In the present work, these inadequacies were targeted using density functional theory-based simulations. Three stable configurations were obtained for the adsorption of thioguanine molecules on the phosphorene surface, with adsorption energies in the range of −76.99 to −38.69 kJ/mol, indicating physisorption of the drug on the phosphorene surface. The calculated bandgap energies of the individual and combined geometries of phosphorene and thioguanine were 0.97 eV, 2.81 eV and 0.91 eV, respectively. Owing to the physisorption of the drug molecule on the phosphorene surface, the bandgap energy of the material had a direct impact on optical conductivity, which was significantly altered. All parameters that determine the potential ability for drug delivery were calculated, such as the dipole moment, chemical hardness, chemical softness, chemical potential, and electrophilicity index. The higher dipole moment (1.74 D) of the phosphorene–thioguanine complex reflects its higher biodegradability, with no adverse physiological effects. Full article
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Case Report
A Case Study Using Accelerometers to Identify Illness in Ewes Following Unintentional Exposure to Mold-Contaminated Feed
Animals 2022, 12(3), 266; https://doi.org/10.3390/ani12030266 (registering DOI) - 21 Jan 2022
Abstract
Sensor technologies can identify modified animal activity indicating changes in health status. This study investigated sheep behavior before and after illness caused by mold-contaminated feed using tri-axial accelerometers. Ten ewes were fitted with HerdDogg biometric accelerometers. Five ewes were concurrently fitted with Axivity [...] Read more.
Sensor technologies can identify modified animal activity indicating changes in health status. This study investigated sheep behavior before and after illness caused by mold-contaminated feed using tri-axial accelerometers. Ten ewes were fitted with HerdDogg biometric accelerometers. Five ewes were concurrently fitted with Axivity AX3 accelerometers. The flock was exposed to mold-contaminated feed following an unexpected ration change, and observed symptomatic ewes were treated with a veterinarian-directed protocol. Accelerometer data were evaluated 4 days before exposure (d −4 to −1); the day of ration change (d 0); and 4 days post exposure (d 1 to 4). Herddogg activity index correlated to the variability of minimum and standard deviation of motion intensity monitored by the Axivity accelerometer. Herddogg activity index was lower (p < 0.05) during the mornings (0800 to 1100 h) of days 2 to 4 and the evening of day 1 than days −4 to 0. Symptomatic ewes had lower activity levels in the morning and higher levels at night. After accounting for symptoms, activity levels during days 1 to 4 were lower (p < 0.05) than days −4 to 0 the morning after exposure. Results suggest real-time or near-real time accelerometers have potential to detect illness in ewes. Full article
Article
Multiclassification Prediction of Clay Sensitivity Using Extreme Gradient Boosting Based on Imbalanced Dataset
Appl. Sci. 2022, 12(3), 1143; https://doi.org/10.3390/app12031143 (registering DOI) - 21 Jan 2022
Abstract
Predicting clay sensitivity is important to geotechnical engineering design related to clay. Classification charts and field tests have been used to predict clay sensitivity. However, the imbalanced distribution of clay sensitivity is often neglected, and the predictive performance could be more accurate. The [...] Read more.
Predicting clay sensitivity is important to geotechnical engineering design related to clay. Classification charts and field tests have been used to predict clay sensitivity. However, the imbalanced distribution of clay sensitivity is often neglected, and the predictive performance could be more accurate. The purpose of this study was to investigate the performance that extreme gradient boosting (XGboost) method had in predicting multiclass of clay sensitivity, and the ability that synthetic minority over-sampling technique (SMOTE) had in addressing imbalanced categories of clay sensitivity. Six clay parameters were used as the input parameters of XGBoost, and SMOTE was used to deal with imbalanced classes. Then, the dataset was divided using the cross-validation (CV) method. Finally, XGBoost, artificial neural network (ANN), and Naive Bayes (NB) were used to classify clay sensitivity. The F1 score, receiver operating characteristic (ROC), and area under the ROC curve (AUC) were considered as the performance indicators. The results revealed that XGBoost showed the best performance in the multiclassification prediction of clay sensitivity. The F1 score and mean AUC of XGBoost were 0.72 and 0.89, respectively. SMOTE was useful in addressing imbalanced issues, and XGBoost was an effective and reliable method of classifying clay sensitivity. Full article
(This article belongs to the Topic Artificial Intelligence (AI) Applied in Civil Engineering)
Review
The Epigenetic Role of Vitamin C in Neurodevelopment
Int. J. Mol. Sci. 2022, 23(3), 1208; https://doi.org/10.3390/ijms23031208 (registering DOI) - 21 Jan 2022
Abstract
The maternal diet during pregnancy is a key determinant of offspring health. Early studies have linked poor maternal nutrition during gestation with a propensity for the development of chronic conditions in offspring. These conditions include cardiovascular disease, type 2 diabetes and even compromised [...] Read more.
The maternal diet during pregnancy is a key determinant of offspring health. Early studies have linked poor maternal nutrition during gestation with a propensity for the development of chronic conditions in offspring. These conditions include cardiovascular disease, type 2 diabetes and even compromised mental health. While multiple factors may contribute to these outcomes, disturbed epigenetic programming during early development is one potential biological mechanism. The epigenome is programmed primarily in utero, and during this time, the developing fetus is highly susceptible to environmental factors such as nutritional insults. During neurodevelopment, epigenetic programming coordinates the formation of primitive central nervous system structures, neurogenesis, and neuroplasticity. Dysregulated epigenetic programming has been implicated in the aetiology of several neurodevelopmental disorders such as Tatton-Brown-Rahman syndrome. Accordingly, there is great interest in determining how maternal nutrient availability in pregnancy might affect the epigenetic status of offspring, and how such influences may present phenotypically. In recent years, a number of epigenetic enzymes that are active during embryonic development have been found to require vitamin C as a cofactor. These enzymes include the ten-eleven translocation methylcytosine dioxygenases (TETs) and the Jumonji C domain-containing histone lysine demethylases that catalyse the oxidative removal of methyl groups on cytosines and histone lysine residues, respectively. These enzymes are integral to epigenetic regulation and have fundamental roles in cellular differentiation, the maintenance of pluripotency and development. The dependence of these enzymes on vitamin C for optimal catalytic activity illustrates a potentially critical contribution of the nutrient during mammalian development. These insights also highlight a potential risk associated with vitamin C insufficiency during pregnancy. The link between vitamin C insufficiency and development is particularly apparent in the context of neurodevelopment and high vitamin C concentrations in the brain are indicative of important functional requirements in this organ. Accordingly, this review considers the evidence for the potential impact of maternal vitamin C status on neurodevelopmental epigenetics. Full article
(This article belongs to the Special Issue New Research on Endocrine Regulation of Brain Development)
Review
Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies
Cancers 2022, 14(3), 547; https://doi.org/10.3390/cancers14030547 (registering DOI) - 21 Jan 2022
Abstract
Tumor relapse represents one of the main obstacles to cancer treatment. Many patients experience cancer relapse even decades from the primary tumor eradication, developing more aggressive and metastatic disease. This phenomenon is associated with the emergence of dormant cancer cells, characterized by cell [...] Read more.
Tumor relapse represents one of the main obstacles to cancer treatment. Many patients experience cancer relapse even decades from the primary tumor eradication, developing more aggressive and metastatic disease. This phenomenon is associated with the emergence of dormant cancer cells, characterized by cell cycle arrest and largely insensitive to conventional anti-cancer therapies. These rare and elusive cells may regain proliferative abilities upon the induction of cell-intrinsic and extrinsic factors, thus fueling tumor re-growth and metastasis formation. The molecular mechanisms underlying the maintenance of resistant dormant cells and their awakening are intriguing but, currently, still largely unknown. However, increasing evidence recently underlined a strong dependency of cell cycle progression to metabolic adaptations of cancer cells. Even if dormant cells are frequently characterized by a general metabolic slowdown and an increased ability to cope with oxidative stress, different factors, such as extracellular matrix composition, stromal cells influence, and nutrient availability, may dictate specific changes in dormant cells, finally resulting in tumor relapse. The main topic of this review is deciphering the role of the metabolic pathways involved in tumor cells dormancy to provide new strategies for selectively targeting these cells to prevent fatal recurrence and maximize therapeutic benefit. Full article
(This article belongs to the Special Issue Tumor and Metabolism)
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Article
Influence of Pre-Hydrolysis on the Chemical Composition of Prunus avium Cherry Seeds
Agronomy 2022, 12(2), 280; https://doi.org/10.3390/agronomy12020280 (registering DOI) - 21 Jan 2022
Abstract
During the industrial processing of sweet cherry fruits, the seeds are considered agricultural waste and must be disposed of, typically through burning. In this context, it is intended to contribute to the scientific development of the ecovalorization of by-products and to provide new [...] Read more.
During the industrial processing of sweet cherry fruits, the seeds are considered agricultural waste and must be disposed of, typically through burning. In this context, it is intended to contribute to the scientific development of the ecovalorization of by-products and to provide new strategies for their transformation into value-added products obtained from sweet cherry seeds (SCS). This work aimed to establish the chemical characterization of SCS before and after several pre-hydrolysis steps in order to allow the solubilization of hemicelluloses that can later be used for the recovery of sugars. The higher percentage of cellulose and lignin remaining in the solid phase will allow its further processing for an integral valorization of the raw material. The temperature (160 and 170 °C) and time (0 and 180 min) of pre-hydrolysis were optimized to obtain the best liquefaction. The percentage of liquefied material was determined from the solid waste obtained at the time of filtration. The best liquefaction by the hydrolysis of SCS was obtained at 170 °C and 180 min, with a yield of 26.7%. The chemical analyses of SCS throughout hydrolysis showed the solubilization of hemicelluloses with increases in the time and temperature of the reactor. -cellulose and lignin showed an increase both with temperature and time, increasing the material’s potential for further processing in adhesives. FTIR analysis showed that there were significant changes in the spectra between the initial SCS, the solid residue, and the liquefied material. Pre-hydrolysis was proven to be an efficient process to improve the chemical composition of the material for further processing into adhesives or higher-mechanical-strength polyurethane foams. Full article
Review
Methods of Measuring Mitochondrial Potassium Channels: A Critical Assessment
Int. J. Mol. Sci. 2022, 23(3), 1210; https://doi.org/10.3390/ijms23031210 (registering DOI) - 21 Jan 2022
Abstract
In this paper, the techniques used to study the function of mitochondrial potassium channels are critically reviewed. The majority of these techniques have been known for many years as a result of research on plasma membrane ion channels. Hence, in this review, we [...] Read more.
In this paper, the techniques used to study the function of mitochondrial potassium channels are critically reviewed. The majority of these techniques have been known for many years as a result of research on plasma membrane ion channels. Hence, in this review, we focus on the critical evaluation of techniques used in the studies of mitochondrial potassium channels, describing their advantages and limitations. Functional analysis of mitochondrial potassium channels in comparison to that of plasmalemmal channels presents additional experimental challenges. The reliability of functional studies of mitochondrial potassium channels is often affected by the need to isolate mitochondria and by functional properties of mitochondria such as respiration, metabolic activity, swelling capacity, or high electrical potential. Three types of techniques are critically evaluated: electrophysiological techniques, potassium flux measurements, and biochemical techniques related to potassium flux measurements. Finally, new possible approaches to the study of the function of mitochondrial potassium channels are presented. We hope that this review will assist researchers in selecting reliable methods for studying, e.g., the effects of drugs on mitochondrial potassium channel function. Additionally, this review should aid in the critical evaluation of the results reported in various articles on mitochondrial potassium channels. Full article
(This article belongs to the Special Issue Intracellular Organellar Ion Channels and Molecular Physiology)
Article
Seaweed Fertilizer Prepared by EM-Fermentation Increases Abundance of Beneficial Soil Microbiome in Paddy (Oryza sativa L.) during Vegetative Stage
Fermentation 2022, 8(2), 46; https://doi.org/10.3390/fermentation8020046 (registering DOI) - 21 Jan 2022
Abstract
Excessive use of chemical fertilizer could potentially decrease soil productivity by decreasing soil microbiome diversity. In this study, we evaluated the effects of fermented seaweed fertilizer in the soil microbial community of paddy plants (Oryza sativa L.). The paddy seedlings were divided [...] Read more.
Excessive use of chemical fertilizer could potentially decrease soil productivity by decreasing soil microbiome diversity. In this study, we evaluated the effects of fermented seaweed fertilizer in the soil microbial community of paddy plants (Oryza sativa L.). The paddy seedlings were divided into five groups, control (C0), chemical fertilizer (CF), seaweed fertilizer (SF), chemical and seaweed fertilizer combination 50:50 (CFSF1), and chemical and fertilizer combination 75:25 (CFSF2). The CFSF1 combination showed to be the most effective in inducing plant height (83.99 ± 3.70 cm) and number of tillers (24.20 ± 4.08). After 8 weeks after transplantation, the isolated DNA from each soil treatment were subjected to 16S rRNA (v3–v4 region) next-generation sequencing. The beneficial Acidobacteriota was most abundant in CFSF1. At genus level, the nitrifying bacteria MND1 was seen to be abundant in CFSF1 and also present in other SF treatments. The genus Chujaibacter is highly abundant in CF, which potentially plays a role in denitrification resulting in soil degradation. In addition, the CFSF1-treated soils show significantly higher diversity of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA). The current results could potentially contribute to the utilization of SF as a bioremediator and promoting green agriculture practice by reducing the amount of CF usage. Full article
(This article belongs to the Special Issue Fermented Products for Agriculture and Bioremediation)
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Review
Emerging Role of Epigenetic Alterations as Biomarkers and Novel Targets for Treatments in Pancreatic Ductal Adenocarcinoma
Cancers 2022, 14(3), 546; https://doi.org/10.3390/cancers14030546 (registering DOI) - 21 Jan 2022
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment options. Emerging evidence shows that epigenetic alterations are present in PDAC. The changes are potentially reversible and therefore promising therapeutic targets. Epigenetic aberrations also influence the tumor microenvironment with the potential to [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment options. Emerging evidence shows that epigenetic alterations are present in PDAC. The changes are potentially reversible and therefore promising therapeutic targets. Epigenetic aberrations also influence the tumor microenvironment with the potential to modulate and possibly enhance immune-based treatments. Epigenetic marks can also serve as diagnostic screening tools, as epigenetic changes occur at early stages of the disease. Further, epigenetics can be used in prognostication. The field is evolving, and this review seeks to provide an updated overview of the emerging role of epigenetics in the diagnosis, treatment, and prognostication of PDAC. Full article
(This article belongs to the Special Issue Epigenetic Detection and Regulation of Cancer Biomarkers)

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