bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Variants at the 9p21.3 Locus Are Associated with Risk for Non-Compressible Artery Disease: Results from the ARTPER Study
Authors: Via Marc , Pera Guillem , Forés Rosa , Costa-Garrido Anna , Heras Antonio , Baena-Díez José Miguel , Pedrosa Edurne , Clemente Inmaculada C. , Lamonja-Vicente Noemí , Mataró Maria , Torán-Montserrat Pere , Alzamora M. Teresa
Published: December 2023

Peripheral artery disease (PAD) and non-compressible artery disease (NCAD) constitute predictors of subclinical atherosclerosis easily assessed through the ankle brachial index (ABI). Although both diseases show substantial genetic influences, few genetic association studies have focused on the ABI and PAD, and none have focused on NCAD. To overcome these limitations, we assessed the role of several candidate genes on the ABI, both in its continuous distribution and in the clinical manifestations associated to its extreme values: PAD and NCAD. We examined 13 candidate genomic regions in 1606 participants from the ARTPER study, a prospective population-based cohort, with the ABI assessed through ultrasonography. Association analyses were conducted independently for individuals with PAD (ABI < 0.9) or with NCAD (ABI > 1.4) vs. healthy participants. After including potential covariates and correction for multiple testing, minor alleles in the genetic markers rs10757278 and rs1333049, both in the 9p21.3 region, were significantly associated with a decreased risk of NCAD. Associations with the ABI showed limited support to these results. No significant associations were detected for PAD. The locus 9p21.3 constitutes the first genetic locus associated with NCAD, an assessment of subclinical atherosclerosis feasible for implementation in primary healthcare settings that has been systematically neglected from genetic studies.
GhCNGC13 and 32 Act as Critical Links between Growth and Immunity in Cotton
Authors: Peng Song , Li Panyu , Li Tianming , Tian Zengyuan , Xu Ruqiang
Published: December 2023

Cyclic nucleotide-gated ion channels (CNGCs) remain poorly studied in crop plants, most of which are polyploid. In allotetraploid Upland cotton (Gossypium hirsutum), silencing GhCNGC13 and 32 impaired plant growth and shoot apical meristem (SAM) development, while triggering plant autoimmunity. Both growth hormones (indole-3-acetic acid and gibberellin) and stress hormones (abscisic acid, salicylic acid, and jasmonate) increased, while leaf photosynthesis decreased. The silenced plants exhibited an enhanced resistance to Botrytis cinerea; however, Verticillium wilt resistance was weakened, which was associated with LIPOXYGENASE2 (LOX2) downregulation. Transcriptomic analysis of silenced plants revealed 4835 differentially expressed genes (DEGs) with functional enrichment in immunity and photosynthesis. These DEGs included a set of transcription factors with significant over-representation in the HSF, NAC, and WRKY families. Moreover, numerous members of the GhCNGC family were identified among the DEGs, which may indicate a coordinated action. Collectively, our results suggested that GhCNGC13 and 32 functionally link to photosynthesis, plant growth, and plant immunity. We proposed that GhCNGC13 and 32 play a critical role in the “growth–defense tradeoff” widely observed in crops.
Copper(II) Complexes with 1-(Isoquinolin-3-yl)heteroalkyl-2-ones: Synthesis, Structure and Evaluation of Anticancer, Antimicrobial and Antioxidant Potential
Authors: Balewski Łukasz , Plech Tomasz , Korona-Głowniak Izabela , Hering Anna , Szczesio Małgorzata , Olczak Andrzej , Bednarski Patrick J. , Kokoszka Jakub , Kornicka Anita
Published: December 2023

Four copper(II) complexes, C1–4, derived from 1-(isoquinolin-3-yl)heteroalkyl-2-one ligands L1–4 were synthesized and characterized using an elemental analysis, IR spectroscopic data as well as single crystal X-ray diffraction data for complex C1. The stability of complexes C1–4 under conditions mimicking the physiological environment was estimated using UV-Vis spectrophotometry. The antiproliferative activity of both ligands L1–4 and copper(II) compounds C1–4 were evaluated using an MTT assay on four human cancer cell lines, A375 (melanoma), HepG2 (hepatoma), LS-180 (colon cancer) and T98G (glioblastoma), and a non-cancerous cell line, CCD-1059Sk (human normal skin fibroblasts). Complexes C1–4 showed greater potency against HepG2, LS180 and T98G cancer cell lines than etoposide (IC50 = 5.04–14.89 μg/mL vs. IC50 = 43.21–>100 μg/mL), while free ligands L1–4 remained inactive in all cell lines. The prominent copper(II) compound C2 appeared to be more selective towards cancer cells compared with normal cells than compounds C1, C3 and C4. The treatment of HepG2 and T98G cells with complex C2 resulted in sub-G1 and G2/M cell cycle arrest, respectively, which was accompanied by DNA degradation. Moreover, the non-cytotoxic doses of C2 synergistically enhanced the cytotoxic effects of chemotherapeutic drugs, including etoposide, 5-fluorouracil and temozolomide, in HepG2 and T98G cells. The antimicrobial activities of ligands L2–4 and their copper(II) complexes C2–4 were evaluated using different types of Gram-positive bacteria, Gram-negative bacteria and yeast species. No correlation was found between the results of the antiproliferative and antimicrobial experiments. The antioxidant activities of all compounds were determined using the DPPH and ABTS radical scavenging methods. Antiradical tests revealed that among the investigated compounds, copper(II) complex C4 possessed the strongest antioxidant properties. Finally, the ADME technique was used to determine the physicochemical and drug-likeness properties of the obtained complexes.
Release of Pro-Inflammatory/Angiogenic Factors by Retinal Microvascular Cells Is Mediated by Extracellular Vesicles Derived from M1-Activated Microglia
Authors: Beltramo Elena , Mazzeo Aurora , Porta Massimo
Published: December 2023

The interactions between the neuronal and vascular sides of the retina during diabetic retinopathy (DR) have gained increasing attention. Microglia is responsible for the immune response to inflammation inside the retina, which could be mediated by paracrine signals carried by extracellular vesicles (EVs). We aimed to characterize EVs released from immortalized human microglial cells in inflammation and investigate their effects on the retinal microvasculature and the anti-inflammatory potential of thiamine in this context. M1 pro-inflammatory polarization in microglia was induced through a cytokine cocktail. EVs were isolated from the supernatants, characterized, and used to stimulate human retinal endothelial cells (HRECs) and pericytes (HRPs). Microvascular cell functions and their release of pro-inflammatory/angiogenic factors were assessed. M1-derived EVs showed increased content of miR-21, miR-155, CCL2, MMP2, and MMP9, and enhanced apoptosis, proliferation, migration, and ROS production in HRPs and HRECs. IL-1β, IL-6, MMP9, CCL2, and VEGF release increased in HRPs exposed to M1-derived EVs, while HRECs showed augmented IL-6, Ang2, VEGF, and PDFG-B. Addition of thiamine to M1-microglial cultures reverted most of these effects. In conclusion, M1-derived EVs stimulate functional changes and secretion of pro-inflammatory/angiogenic molecules in microvascular cells, exacerbating inflammatory damage and retinopathy features. Thiamine added to microglia exerts anti-inflammatory effects.
[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones
Authors: Kuznetsova Juliana V. , Tkachenko Varvara T. , Petrovskaya Lada M. , Filkina Maria E. , Shybanov Dmitry E. , Grishin Yuri K. , Roznyatovsky Vitaly A. , Tafeenko Viktor A. , Pestretsova Anna S. , Yakovleva Vera A. , Pokrovsky Vadim S. , Kukushkin Maxim E. , Beloglazkina Elena K.
Published: December 2023

Approximately 1,3-Dipolar cycloaddition of imidazolidine derivatives containing exocyclic double bonds is a convenient method of creating spiro-conjugated molecules with promising anticancer activity. In this work, the derivatives of parabanic acid (2-thioxoimidazolidine-4,5-diones and 5-aryliminoimidazolidine-2,4-diones) were first investigated as dipolarophiles in the reactions with nitrile imines. The generation of nitrile imines was carried out either by the addition of tertiary amine to hydrazonoyl chlorides «drop by drop» or using the recently proposed diffusion mixing technique, which led to ~5–15% increases in target compound yields. It was found that the addition of nitrile imines to C=S or C=N exocyclic double bonds led to 1,2,4-thiazolines or triazolines and occurred regioselectively in accordance with the ratio of FMO coefficients of reactants. The yield of the resulting spiro-compound depended on the presence of alkyl substituents in the nitrile imine structure and was significantly decreased in reactions with imines with strong electron donor or electron-withdrawing groups. Some of the obtained compounds showed reasonable in vitro cytotoxicity. IC50 values were calculated for HCT116 (colon cancer) cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test.
Genome-Wide Identification of the CBF Gene Family and ICE Transcription Factors in Walnuts and Expression Profiles under Cold Conditions
Authors: Zhou Huijuan , Ma Jiayu , Liu Hengzhao , Zhao Peng
Published: December 2023

Cold stress impacts woody tree growth and perennial production, especially when the temperature rapidly changes in late spring. To address this issue, we conducted the genome-wide identification of two important transcription factors (TFs), CBF (C-repeat binding factors) and ICE (inducers of CBF expression), in three walnut (Juglans) genomes. Although the CBF and ICE gene families have been identified in many crops, very little systematic analysis of these genes has been carried out in J. regia and J. sigillata. In this study, we identified a total of 16 CBF and 12 ICE genes in three Juglans genomes using bioinformatics analysis. Both CBF and ICE had conserved domains, motifs, and gene structures, which suggests that these two TFs were evolutionarily conserved. Most ICE genes are located at both ends of the chromosomes. The promoter cis-regulatory elements of CBF and ICE genes are largely involved in light and phytohormone responses. Based on 36 RNA sequencing of leaves from four walnut cultivars (‘Zijing’, ‘Lvling’, ‘Hongren’, and ‘Liao1’) under three temperature conditions (8 °C, 22 °C, and 5 °C) conditions in late spring, we found that the ICE genes were expressed more highly than CBFs. Both CBF and ICE proteins interacted with cold-related proteins, and many putative miRNAs had interactions with these two TFs. These results determined that CBF1 and ICE1 play important roles in the tolerance of walnut leaves to rapid temperature changes. Our results provide a useful resource on the function of the CBF and ICE genes related to cold tolerance in walnuts.
Our Mental Health Is Determined by an Intrinsic Interplay between the Central Nervous System, Enteric Nerves, and Gut Microbiota
Authors: Dicks Leon M. T.
Published: December 2023

Bacteria in the gut microbiome play an intrinsic part in immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling. The gut microbiota communicates with the central nervous system (CNS) through the production of bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT), and histamine. A vast number of signals generated in the gastrointestinal tract (GIT) reach the brain via afferent fibers of the vagus nerve (VN). Signals from the CNS are returned to entero-epithelial cells (EES) via efferent VN fibers and communicate with 100 to 500 million neurons in the submucosa and myenteric plexus of the gut wall, which is referred to as the enteric nervous system (ENS). Intercommunications between the gut and CNS regulate mood, cognitive behavior, and neuropsychiatric disorders such as autism, depression, and schizophrenia. The modulation, development, and renewal of nerves in the ENS and changes in the gut microbiome alter the synthesis and degradation of neurotransmitters, ultimately influencing our mental health. The more we decipher the gut microbiome and understand its effect on neurotransmission, the closer we may get to developing novel therapeutic and psychobiotic compounds to improve cognitive functions and prevent mental disorders. In this review, the intricate control of entero-endocrine signaling and immune responses that keep the gut microbiome in a balanced state, and the influence that changing gut bacteria have on neuropsychiatric disorders, are discussed.
Insights into the Cellular Localization and Functional Properties of TSPYL5 Protein
Authors: Silonov Sergey A. , Smirnov Eugene Y. , Shmidt Eva A. , Kuznetsova Irina M. , Turoverov Konstantin K. , Fonin Alexander V.
Published: December 2023

In recent years, the role of liquid–liquid phase separation (LLPS) and intrinsically disordered proteins (IDPs) in cellular molecular processes has received increasing attention from researchers. One such intrinsically disordered protein is TSPYL5, considered both as a marker and a potential therapeutic target for various oncological diseases. However, the role of TSPYL5 in intracellular processes remains unknown, and there is no clarity even in its intracellular localization. In this study, we characterized the intracellular localization and exchange dynamics with intracellular contents of TSPYL5 and its parts, utilizing TSPYL5 fusion proteins with EGFP. Our findings reveal that TSPYL5 can be localized in both the cytoplasm and nucleoplasm, including the nucleolus. The nuclear (nucleolar) localization of TSPYL5 is mediated by the nuclear/nucleolar localization sequences (NLS/NoLS) identified in the N-terminal intrinsically disordered region (4–27 aa), while its cytoplasmic localization is regulated by the ordered NAP-like domain (198–382 aa). Furthermore, our results underscore the significant role of the TSPYL5 N-terminal disordered region (1–198 aa) in the exchange dynamics with the nucleoplasm and its potential ability for phase separation. Bioinformatics analysis of the TSPYL5 interactome indicates its potential function as a histone and ribosomal protein chaperone. Taken together, these findings suggest a significant contribution of liquid–liquid phase separation to the processes involving TSPYL5, providing new insights into the role of this protein in the cell’s molecular life.
Relationship between the Status of Third Molars and the Occurrence of Dental and Periodontal Lesions in Adjacent Second Molars in the Polish Population: A Radiological Retrospective Observational Study
Authors: Poszytek Daniel , Górski Bartłomiej
Published: December 2023

The aim of this study was to evaluate the effect of third molars on caries, external root resorption, and alveolar bone loss on the distal surface of adjacent second molars. A total of 2488 panoramic radiographs of adult Poles were evaluated. Third molars were classified, according to eruption status, into non-impacted, partially, or completely impacted, and according to angulation into horizontal, mesioangular, vertical, and distoangular. Completely impacted third molars were assigned as reference group. The odds ratios (ORs) and 95% confidence intervals for the occurrence of the above-mentioned pathologies were 1.39 (1.09–2.21), 6.51 (3.72–10.11), and 2.42 (1.22–4.09), respectively, for second molars with adjacent erupted third molars and 1.54 (1.11–2.82), 10.65 (7.81–20.19), and 5.21 (3.38–10.81), respectively, when partially impacted third molars were next to second molars. The ORs of lesions were significantly higher for horizontally and mesioangularly impacted third molars. Within the limitation of a radiological study, it might be concluded that the presence of erupted third molars is a risk factor for caries, while the presence of impacted third molars increases the risk of root resorption and bone loss on the distal surface of second molars.
Barriers to Adherence to Healthy Diet and Recommended Physical Activity Perceived by the Polish Population
Authors: Domosławska-Żylińska Katarzyna , Łopatek Magdalena , Krysińska-Pisarek Magdalena , Sugay Larysa
Published: December 2023

Background: According to the World Health Organization, an unhealthy diet and lack of physical activity constitute the primary global health risks. The purpose of this study was to as-certain the barriers to a healthy diet (HD) and physical activity (PA) as perceived by the Polish population in order to implement public health interventions. Methods: A quantitative survey was conducted using the computer-assisted telephone interview technique on a randomly selected representative sample of 2000 Polish citizens aged 18–88 years. The research tool was a questionnaire consisting of two parts: sociodemographic characteristics and examining barriers to an HD (Cronbach’s alpha = 0.899) and regular PA (Cronbach’s alpha = 0.923). Results: Women constituted more than half of the sample (53.4%), and most of the respondents lived in urban areas (60.5%), considered their financial situation as average (56.9%), and their health as satisfactory (42.3%). Barriers to an HD include the cost of healthy food (43%), lack of motivation (26.7%), and lack of time (25.4%). Barriers to taking up PA include competing priorities (29%), a lack of motivation to exercise (27.3%), feeling of constant fatigue, and lack of energy (24.4%). Limiting factors in the adoption of both an HD and PA are gender (women > men; HD p < 0.01; PA p < 0.001), financial situation (unsatisfactory; HD and PA p < 0.001), health condition (unsatisfactory; HD and PA p < 0.001), type of work (blue-collar workers; HD p < 0.001; PA p < 0.05), and employment status (people running household; HD and PA p < 0.001). Conclusions: The results of this study provide important information about barriers to adopting healthy lifestyle principles. The practical implications of our work can be used by policymakers responsible for intervention strategies and programmes to increase the number of people adhering to recommendations for an HD and PA by removing barriers.
Specimen Shape and Elution Time Affect the Mineralization and Differentiation Potential of Dental Pulp Stem Cells to Biodentine
Authors: Phang Valene , Malhotra Ritika , Chen Nah Nah , Min Kyung-San , Yu Victoria Soo Hoon , Rosa Vinicius , Dubey Nileshkumar
Published: December 2023

The liquid extract method is commonly used to evaluate the cytotoxicity and bioactivity of materials. Although ISO has recommended guidelines for test methods, variations in elution period, and shape of samples can influence the biological outcomes. The aim of this study was to investigate the influence of material form and elution period of Biodentine on dental pulp stem cells (DPSCs)’ proliferation and mineralization. Biodentine (0.2 g) discs or powder were immersed in culture media (10 mL) for 1, 3 or 7 days (D1, D3 and D7). The eluents were filtered and used to treat DPSC. The calcium release profile and pH were determined. Cell proliferation was evaluated by MTS for 3 days, and mineralization and differentiation were assessed by alizarin red S staining (Ca2+/ng of DNA) and qRT-PCR (MEPE, DSPP, DMP-1, RUNX2, COL-I and OCN) for 14 days. Statistical analysis was performed with a one or two-way ANOVA and post hoc Tukey’s test (pH, calcium release and proliferation) or Mann–Whitney test (α = 0.05). pH and calcium ion release of powdered eluents were significantly higher than disc eluents. Powdered eluent promoted extensive cell death, while the disc form was cytocompatible. All disc eluents significantly increased the gene expression and mineralization after 14 days compared to the untreated control. D7 induced less mineralization and differentiation compared to D1 and D3. Thus, the materials’ form and elution time are critical aspects to be considered when evaluating the bioactivity of materials, since this binomial can affect positively and negatively the biological outcomes.
Extended Time Window (>6 Hour) Mechanical Thrombectomy; Good Clinical Outcome in the Younger Age Population in Thrombectomy Cases: Relationship between Age and Prognosis
Authors: Gok Deok Un , Kim So Yeon , Na Young Chul , Cho Jin Mo
Published: December 2023

Background: Mechanical thrombectomy (MT) has become increasingly common in recent years, as studies have shown that it can be an effective treatment for acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). However, the efficacy of MT in the extended time window (6 to 24 h) is still uncertain. Our study aims to evaluate the outcomes of MT in the extended time window for AIS patients. Methods: We reviewed data on AIS patients who received MT beyond six hours of stroke onset from 2015 to 2022. The patients’ occlusions were in the internal carotid artery (ICA), middle cerebral artery (MCA), or posterior circulation. Our evaluation included the modified Rankin scale (mRS) and 90-day mortality rates, as well as complications, such as symptomatic intracranial hemorrhage (sICH). Results: Thirty-one patients were included in this study, with a mean age of 75.6 ± 15.1 years, of whom 54.8% were male. The median NIHSS score at presentation was 17. Successful recanalization (TICI 2b to 3) was achieved in 90.3% of patients and the rate of sICH was 6.4%. No difference was observed between the two age groups. The younger age group (<80 years old) showed a better clinical outcome (mRS 0–2; p < 0.05, Fisher’s exact test) compared with the older age group. The overall mortality rate was 6.4%. Conclusion: Our study shows that (MT) can be performed effectively and safely within an extended time window, resulting in satisfactory functional outcomes, particularly in the younger age group.
Carbon Farming: How to Support Farmers in Choosing the Best Management Strategies for Low-Impact Food Production
Authors: Piscitelli Lea , De Boni Annalisa , Roma Rocco , Ottomano Palmisano Giovanni
Published: December 2023

The European Commission is directing efforts into triggering the storage of carbon in agricultural soils by encouraging the adoption of carbon farming practices under the European Green Deal and in other key EU policies. However, farmers that want to enter this production model urgently need to define the sustainable practices required for increasing soil organic carbon without overturning production systems and also need to adapt it for optimizing yields and improving carbon stocks. However, there is still a lack of tools that are easy to use and interpret for guiding farmers and stakeholders to find ways in which to increase soil organic carbon content. Therefore, this research aims to set up a novel bottom–up approach, in terms of the methodology and analysis process, for identifying tailored sustainable farming management strategies for the purpose of increasing soil carbon. We investigated 115 real food production cases that were carried out under homogeneous pedo-climatic conditions over a period of 20 years in the Apulia region (Southern Italy), which made it possible to create a dataset of 12 variables that were analyzed through a decision tree (created with the C4.5 algorithm). The overall results highlight that the treatment duration was the most crucial factor and affected the carbon stock both positively and negatively. This was followed by the use of cover crops alone and then those in combination with a type of irrigation system; hence, specific agricultural management strategies were successfully identified for obtaining effective carbon storage in the considered real food production cases. From a wider perspective, this research can serve as guidance to help EU private actors and public authorities to start carbon farming initiatives, pilot projects, or certification schemes at the local and/or regional levels.
Relationship between Eating Habits and 4-Nonylphenol Concentration in Breast Milk of Women in Slovakia
Authors: Repková Adriana , Mišľanová Csilla , Hrabčáková Janka , Masár Marián , Slezáková Zuzana , Žemlička Lukáš , Valachovičová Martina
Published: December 2023

4-Nonylphenol belongs to the alkylphenol group of chemicals, and its high occurrence in the environment can cause an adverse effect on human health. Breast milk can serve as a marker to take measure of human exposure to these chemicals through different routes of exposure. In this work, the influence of selected factors (the kind of water drank by the mothers; the consumption of fish, pork, and beef; wearing gloves; using nail polish, gel nails, vitamins, and medication) on the concentration on 4-nonylphenol in 89 breast milk samples was studied. The concentrations of nonylphenol in breast milk were determined by HPLC with fluorescence detection. The lowest and highest concentrations of 4-nonylphenol in breast milk were 0.97 ng/mL and 4.37 ng/mL, respectively. Statistical significance was observed for the consumption of pork (p = 0.048) and fish (0.041) in relation to the 4-nonylphenol concentration. Certain parameters (use of gel nails, beef consumption, and vitamin supplementation) were at the border of statistical significance (p = 0.06). Other parameters did not show any statistical significance. The results showed that breast milk in Slovakia does not contain a harmful dose of 4-nonylphenol and does not cause health problems. But it is necessary to continue this research and perform extended screening on a larger number of samples.
Experimental Study on Tensile Performance of FRP Tendons/Cables with Varied Bond Anchorage Factors
Authors: Zhao Xing , Meng Lanjinhua , Li Sihao
Published: December 2023

FRP tendons and cables are increasingly being used in civil engineering structures due to their high strength-to-weight ratio and corrosion resistance. The bond anchorage factors, which characterize the bond strength between the FRP tendon/cable and the surrounding materials, play a critical role in determining the overall performance of the system. In this study, a series of tensile tests were conducted on FRP tendons/cables with different bond anchorage factors to evaluate their load-carrying capacity, load–displacement curve, and strain distribution. The study considered different types and surface shapes of FRP tendons/cables, and determined the influence of anchoring length, bonding medium type, and bonding medium thickness on the performance. The strain distribution of FRP tendons/cables at the anchorage end gradually increased along the loading section to the free end. A stress analysis model of the anchoring section was proposed and found to be consistent with the test results.
Fe- and S-Modified BiOI as Catalysts to Oxygen Evolution and Hydrogen Evolution Reactions in Overall Photoelectrochemical Water Splitting
Authors: Lei Yu , Chen Hongdian , Shu Chenyang , Chen Changguo
Published: December 2023

Developing catalysts with superior activity to hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is equally important to the overall photoelectrochemical water splitting to produce hydrogen. In this work, bismuth oxyiodide (BiOI), iron-modified bismuth iodide Fe/BiOI, and the sulfurized S-Fe/BiOI were prepared using the solvothermal method. The three materials all have good absorption ability for visible light. The photoelectrochemical catalytic activity of BiOI to oxygen evolution reaction (OER) is significantly enhanced after iron modification, while the sulfurized product S-Fe/BiOI exhibits better catalytic activity to hydrogen evolution reaction (HER). Hence, OER and HER can be simultaneously catalyzed by using Fe/BiOI and S-Fe/BiOI as anodic and cathodic catalysts to facilitate the overall photoelectrochemical water splitting process.
Estimation of Thermal Stability of Si-SiO2-W Nanolayered Structures with Infrared Spectrometry
Authors: Avotina Liga , Goldmane Annija Elizabete , Zaslavskis Aleksandrs , Romanova Marina , Vanags Edgars , Sorokins Hermanis , Kizane Gunta , Dekhtyar Yuri
Published: December 2023

Nanolayered coatings are proposed for use in microelectronic devices where the size/performance ratio is becoming increasingly important, with the aim to achieve existing quality requirements while reducing the size of the devices and improving their ability to perform stably over multiple cycles. Si-SiO2-W structures have been proposed as a potential material for the fabrication of microelectronic devices. However, before such materials can be implemented in devices, their properties need to be carefully studied. In this study, Si-SiO2-W nanolayered structures were fabricated and subjected to numerous thermal treatment cycles at 150 °C. A total of 33 heating cycles were applied, resulting in a cumulative exposure of 264 h. The changes in chemical bonds and microstructure were monitored using Fourier Transform Infrared spectrometry (FTIR) and scanning electron microscopy (SEM). The FTIR signal at 960 cm−1, indicating the presence of W deposited on SiO2, was selected to characterize the thermal stability during the heating cycles. The estimated signal intensity variation closely resembled the normal inhomogeneity of the nanolayers. The increase in slope intensity was estimated to be 1.7 × 10−5.
Analysis of Crude, Diverse, and Multiple Advanced Glycation End-Product Patterns May Be Important and Beneficial
Authors: Takata Takanobu , Masauji Togen , Motoo Yoshiharu
Published: December 2023

Lifestyle-related diseases (LSRDs), such as diabetes mellitus, cardiovascular disease, and nonalcoholic steatohepatitis, are a global crisis. Advanced glycation end-products (AGEs) have been extensively researched because they trigger or promote LSRDs. Recently, techniques such as fluorimetry, immunostaining, Western blotting, slot blotting, enzyme-linked immunosorbent assay, gas chromatography-mass spectrometry, matrix-assisted laser desorption-mass spectrometry (MALDI-MS), and electrospray ionization-mass spectrometry (ESI-MS) have helped prove the existence of intra/extracellular AGEs and revealed novel AGE structures and their modifications against peptide sequences. Therefore, we propose modifications to the existing categorization of AGEs, which was based on the original compounds identified by researchers in the 20th century. In this investigation, we introduce the (i) crude, (ii) diverse, and (iii) multiple AGE patterns. The crude AGE pattern is based on the fact that one type of saccharide or its metabolites or derivatives can generate various AGEs. Diverse and multiple AGE patterns were introduced based on the possibility of combining various AGE structures and proteins and were proven through mass analysis technologies such as MALDI-MS and ESI-MS. Kampo medicines are typically used to treat LSRDs. Because various compounds are contained in Kampo medicines and metabolized to exert effects on various organs or tissues, they may be suitable against various AGEs.
Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPARα/CPT1 in AML12 Cells
Authors: Liu Yu-Chen , Wei Gang , Liao Zhi-Qiang , Wang Fang-Xin , Zong Chunxiao , Qiu Jiannan , Le Yifei , Yu Zhi-Ling , Yang Seo Young , Wang Heng-Shan , Dou Xiao-Bing , Wang Cai-Yi
Published: December 2023

Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.
Broad-Spectrum Antibody-Based Immunochromatographic Strip Assay for Rapid Screening of Bisphenol A Diglycidyl Ether and Its Derivatives in Canned Foods
Authors: Yu Chundi , Hu Jinnuo , Wu Wei , Zhou Yongfei , Zhang Can , Yang Qingli
Published: December 2023

Bisphenol A diglycidyl ether (BADGE) is widely present in the inner coating of metal food cans, from which it can migrate into food and generate harmful derivatives during storage, such as bisphenol A (2,3-dihydroxypropyl) glycidyl ether, bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether, and bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) glycidyl ether. Here, a gold-nanoparticle-based immunochromatographic strip assay based on a broad-spectrum polyclonal antibody was developed for the simultaneous detection of BADGE and its derivatives, which could be accomplished within 15 min. The quantitative analysis of the visualization results was performed using Adobe Photoshop CC 2021, and the detection limit, defined as the concentration causing 15% inhibition, was 0.97 ng/mL. The recoveries of BADGE and its derivatives at various spiking levels in canned food samples ranged from 79.86% to 93.81%. The detection results of the proposed immunochromatographic strip assay were validated via high-performance liquid chromatography, showing a good correlation coefficient (R2 = 0.9580).
Synthesis and Activity Evaluation of Vinpocetine-Derived Indole Alkaloids
Authors: Dong Zhang-Chao , Shi Yang , Zheng Liang-Liang , Tian You-Ping , Yang Jian , Wei Ying , Zhou Ying , Pan Bo-Wen
Published: December 2023

This study focuses on the synthesis of novel vinpocetine derivatives (2–25) and their biological evaluation. The chemical structures of the synthesized compounds were fully characterized using techniques such as 1H NMR, 13C NMR, and HRMS. The inhibitory activity of the synthesized compounds on PDE1A was evaluated, and the results revealed that compounds 3, 4, 5, 12, 14, 21, and 25 exhibited superior inhibitory activity compared to vinpocetine. Compound 4, with a para-methylphenyl substitution, showed a 5-fold improvement in inhibitory activity with an IC50 value of 3.53 ± 0.25 μM. Additionally, compound 25, with 3-chlorothiazole substitution, displayed an 8-fold increase in inhibitory activity compared to vinpocetine (IC50 = 2.08 ± 0.16 μM). Molecular docking studies were conducted to understand the binding models of compounds 4 and 25 within the active site of PDE1A. The molecular docking study revealed additional binding interactions, such as π–π stacking and hydrogen bonding, contributing to the enhanced inhibitory activity and stability of the ligand–protein complexes. Overall, the synthesized vinpocetine derivatives demonstrated promising inhibitory activity on PDE1A, and the molecular docking studies provided insights into their binding modes, supporting further development of these compounds as potential candidates for drug research and development.
1-Hydroxyalkylphosphonium Salts—Synthesis and Properties
Authors: Adamek Jakub , Kuźnik Anna , Październiok-Holewa Agnieszka , Grymel Mirosława , Kozicka Dominika , Mierzwa Dominika , Erfurt Karol
Published: December 2023

An efficient and convenient method for the synthesis of 1-hydroxyalkylphosphonium salts is described. Reactions were carried out at room temperature, in a short time, and without chromatography for product isolation. The properties of the obtained phosphonium salts were examined and discussed. In this paper, primary attention was paid to the stability of phosphonium salts, depending on the structure of the aldehydes used as substrates in their preparation. Other conditions such as the type of solvent, temperature, and molar ratio of the substrates were also investigated. Finally, the high reactivity of 1-hydroxyalkylphosphonium salts was demonstrated in reactions with amide-type substrates and (hetero)aromatic compounds. The developed step-by-step procedure (with the isolation of 1-hydroxyphosphonium salts) was compared to the one-pot protocol (in situ formation of such phosphonium salts).
Citric Acid: Properties, Microbial Production, and Applications in Industries
Authors: Książek Ewelina
Published: December 2023

Citric acid finds broad applications in various industrial sectors, such as the pharmaceutical, food, chemical, and cosmetic industries. The bioproduction of citric acid uses various microorganisms, but the most commonly employed ones are filamentous fungi such as Aspergillus niger and yeast Yarrowia lipolytica. This article presents a literature review on the properties of citric acid, the microorganisms and substrates used, different fermentation techniques, its industrial utilization, and the global citric acid market. This review emphasizes that there is still much to explore, both in terms of production process techniques and emerging new applications of citric acid.
Bacterial, Fungal, and Parasitic Zoonoses
Authors: Ebani Valentina Virginia , Mancianti Francesca
Published: December 2023

Zoonoses encompass several bacterial, parasitic, and mycotic diseases of domestic and free-living animals [...]
Inhalation of Pelargonium graveolens Essential Oil Alleviates Pain and Related Anxiety and Stress in Patients with Lumbar Spinal Stenosis and Moderate to Severe Pain
Authors: Seo Eunhye , Cho Yoonah , Lee Jeong-Min , Seol Geun Hee
Published: December 2023

Pain in lumbar spinal stenosis (LSS) patients is closely associated with psychological factors, including anxiety, stress, and depression, and is a critical determinant of patient daily functionality and overall quality of life. The present study evaluated the effects of inhalation of Pelargonium graveolens (geranium) essential oil (GEO) on pain and related psychological factors in LSS patients. Fifty-nine patients, categorized as having mild or moderate to severe pain based on pain visual analog scale (VAS) scores, were randomly assigned to inhalation of 1% GEO or placebo control (PC). No significant differences between GEO and PC were observed in patients with mild pain, whereas differences in anxiety-VAS and stress-VAS scores were observed in patients with moderate to severe pain. Anxiety-VAS and stress-VAS scores decreased significantly after GEO but not after PC inhalation. Regardless of the severity of pain, post-intervention pain-VAS scores were significantly lower in the GEO group than in the PC group. In summary, GEO reduced pain and improved anxiety and stress, particularly among patients with moderate to severe pain. These findings suggest that GEO inhalation may have potential as an adjunct therapy for improving pain management and alleviating anxiety and stress in LSS patients with insufficient responses to pharmacological pain control.
Cell Membrane-Derived Nanovehicles for Targeted Therapy of Ischemic Stroke: From Construction to Application
Authors: Hao Cui , Sha Ma , Ye Yang , Wang Chengxiao
Published: December 2023

Ischemic stroke (IS) is a prevalent form of stroke and a leading cause of mortality and disability. Recently, cell membrane-derived nanovehicles (CMNVs) derived from erythrocytes, thrombocytes, neutrophils, macrophages, neural stem cells, and cancer cells have shown great promise as drug delivery systems for IS treatment. By precisely controlling drug release rates and targeting specific sites in the brain, CMNVs enable the reduction in drug dosage and minimization of side effects, thus significantly enhancing therapeutic strategies and approaches for IS. While there are some reviews regarding the applications of CMNVs in the treatment of IS, there has been limited attention given to important aspects such as carrier construction, structural design, and functional modification. Therefore, this review aims to address these key issues in CMNVs preparation, structural composition, modification, and other relevant aspects, with a specific focus on targeted therapy for IS. Finally, the challenges and prospects in this field are discussed.
Nano-Drug Delivery Systems in Oral Cancer Therapy: Recent Developments and Prospective
Authors: Zhang Yun , Wu Yongjia , Du Hongjiang , Li Zhiyong , Bai Xiaofeng , Wu Yange , Li Huimin , Zhou Mengqi , Cao Yifeng , Chen Xuepeng
Published: December 2023

Oral cancer (OC), characterized by malignant tumors in the mouth, is one of the most prevalent malignancies worldwide. Chemotherapy is a commonly used treatment for OC; however, it often leads to severe side effects on human bodies. In recent years, nanotechnology has emerged as a promising solution for managing OC using nanomaterials and nanoparticles (NPs). Nano-drug delivery systems (nano-DDSs) that employ various NPs as nanocarriers have been extensively developed to enhance current OC therapies by achieving controlled drug release and targeted drug delivery. Through searching and analyzing relevant research literature, it was found that certain nano-DDSs can improve the therapeutic effect of drugs by enhancing drug accumulation in tumor tissues. Furthermore, they can achieve targeted delivery and controlled release of drugs through adjustments in particle size, surface functionalization, and drug encapsulation technology of nano-DDSs. The application of nano-DDSs provides a new tool and strategy for OC therapy, offering personalized treatment options for OC patients by enhancing drug delivery, reducing toxic side effects, and improving therapeutic outcomes. However, the use of nano-DDSs in OC therapy still faces challenges such as toxicity, precise targeting, biodegradability, and satisfying drug-release kinetics. Overall, this review evaluates the potential and limitations of different nano-DDSs in OC therapy, focusing on their components, mechanisms of action, and laboratory therapeutic effects, aiming to provide insights into understanding, designing, and developing more effective and safer nano-DDSs. Future studies should focus on addressing these issues to further advance the application and development of nano-DDSs in OC therapy.
Toxicity Evaluation and Controlled-Release of Curcumin-Loaded Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles: In Vitro and In Vivo Models
Authors: Luss Anna L. , Bagrov Dmitry V. , Yagolovich Anne V. , Kukovyakina Ekaterina V. , Khan Irina I. , Pokrovsky Vadim S. , Shestovskaya Maria V. , Gasparian Marine E. , Dolgikh Dmitry A. , Kuskov Andrey N.
Published: December 2023

Curcumin attracts huge attention because of its biological properties: it is antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems, we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the solvent evaporation method and were characterized by dynamic and electrophoretic light scattering, transmission electron (TEM) and atomic force (AFM) microscopy. The average particle size was 200 nm, and the ζ-potential was −4 mV. Curcumin-release studies showed that nanoparticles are stable in aqueous solutions. An in vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently, and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to free curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. The median lethal dose was determined in an acute toxicity assay on zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment.
Spatial O2 Profile in Coix lacryma-jobi and Sorghum bicolor along the Gas Diffusion Pathway under Waterlogging Conditions
Authors: Tamaru Shotaro , Goto Keita , Sakagami Jun-Ichi
Published: December 2023

While internal aeration in plants is critical for adaptation to waterlogging, there is a gap in understanding the differences in oxygen diffusion gradients from shoots to roots between hypoxia-tolerant and -sensitive species. This study aims to elucidate the differences in tissue oxygen concentration at various locations on the shoot and root between a hypoxia-tolerant species and a -sensitive species using a microneedle sensor that allows for spatial oxygen profiling. Job’s tears, a hypoxia-tolerant species, and sorghum, a hypoxia-susceptible species, were tested. Plants aged 10 days were acclimated to a hypoxic agar solution for 12 days. Oxygen was profiled near the root tip, root base, root shoot junction, stem, and leaf. An anatomical analysis was also performed on the roots used for the O2 profile. The oxygen partial pressure (pO2) values at the root base and tip of sorghum were significantly lower than that of the root of Job’s tears. At the base of the root of Job’s tears, pO2 rapidly decreased from the root cortex to the surface, indicating a function to inhibit oxygen leakage. No significant differences in pO2 between the species were identified in the shoot part. The root cortex to stele ratio was significantly higher from the root tip to the base in Job’s tears compared to sorghum. The pO2 gradient began to differ greatly at the root shoot junction and root base longitudinally, and between the cortex and stele radially, between Job’s tears and sorghum. Differences in the root oxygen retention capacity and the cortex to stele ratio are considered to be related to differences in pO2.
Facilitated Transport across Glycocalyceal Barriers in the Chick Chorioallantoic Membrane
Authors: Dayal Anuhya , Pan Jennifer M. , Kwan Stacey P. , Ackermann Maximilian , Khalil Hassan A. , Mentzer Steven J.
Published: December 2023

Targeted drug delivery to visceral organs offers the possibility of not only limiting the required dose, but also minimizing drug toxicity; however, there is no reliable method for delivering drugs to the surface of visceral organs. Here, we used six color tracers and the chick chorioallantoic membrane (CAM) model to investigate the use of the heteropolysaccharide pectin to facilitate tracer diffusion across the glycocalyceal charge barrier. The color tracers included brilliant blue, Congo red, crystal violet, indocyanine green, methylene blue, and methyl green. The direct application of the tracers to the CAM surface or embedding tracers into linear-chain nanocellulose fiber films resulted in no significant diffusion into the CAM. In contrast, when the tracers were actively loaded into branched-chain pectin films, there was significant detectable diffusion of the tracers into the CAM. The facilitated diffusion was observed in the three cationic tracers but was limited in the three anionic tracers. Diffusion appeared to be dependent on ionic charge, but independent of tracer size or molecular mass. We conclude that dye-loaded pectin films facilitated the diffusion of color tracers across the glycocalyceal charge barrier and may provide a therapeutic path for drug delivery to the surface of visceral organs.