bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Progress of Three-Dimensional Graphene-Based Composites for Photocatalysis
Authors: Zhang Fengling , Liu Jianxing , Hu Liang , Guo Cean
Published: September 2024

Converting solar energy into fuels/chemicals through photochemical approaches holds significant promise for addressing global energy demands. Currently, semiconductor photocatalysis combined with redox techniques has been intensively researched in pollutant degradation and secondary energy generation owing to its dual advantages of oxidizability and reducibility; however, challenges remain, particularly with improving conversion efficiency. Since graphene’s initial introduction in 2004, three-dimensional (3D) graphene-based photocatalysts have garnered considerable attention due to their exceptional properties, such as their large specific surface area, abundant pore structure, diverse surface chemistry, adjustable band gap, and high electrical conductivity. Herein, this review provides an in-depth analysis of the commonly used photocatalysts based on 3D graphene, outlining their construction strategies and recent applications in photocatalytic degradation of organic pollutants, H2 evolution, and CO2 reduction. Additionally, the paper explores the multifaceted roles that 3D graphene plays in enhancing photocatalytic performance. By offering a comprehensive overview, we hope to highlight the potential of 3D graphene as an environmentally beneficial material and to inspire the development of more efficient, versatile graphene-based aerogel photocatalysts for future applications.
Next-Generation Sequencing to Determine Changes in the Intestinal Microbiome of Juvenile Sturgeon Hybrid (Acipenser gueldenstaedtii♀ × Acipenser baerii♂) Resulting from Sodium Butyrate, Β-Glucan and Vitamin Supplementation
Authors: Arciuch-Rutkowska Martyna , Nowosad Joanna , Łuczyński Michał Krzysztof , Hussain Syed Makhdoom , Kucharczyk Dariusz
Published: September 2024

Background/Objectives: The effect of sodium butyrate (NaB), β-glucan (βG) and vitamins in the diet on gut microbiome, cortisol level, lysozyme activity and growth parameters of juvenile hybrid sturgeon (Acipenser gueldenstaedtii♀ × Acipenser baerii♂) was determined. Methods: Sturgeon hybrids (n = 144) were divided into three groups with enriched feeding (mg/kg of feed): FQV1 (50 NaB; 20 βG; const. vitamins), FQV2 (150 NaB; 20 βG; const. vitamins), FQV3 (50 NaB; 60 βG; const. vitamins) and control (not supplemented), each group in triplicate, 12 fish in each repetition. Rearing was carried out for 30 days in controlled conditions. Gut microbiome was characterized using Next Generation Sequencing (NGS) of DNA samples isolated from intestinal content. Cortisol level was determined using the ELISA test. Lysozyme activity was measured by turbidimetric test. Results: Based on data obtained from NGS, it was determined that the FQV1 group is characterized by the highest values of diversity indices (Shannon, Simpson and Chao-1) and the largest number of ASVs (Amplicon Sequence Variants). The highest abundance of probiotic bacteria (Lactobacillus, Lactococcus) was determined in the FQV1 group. The highest cortisol concentration was determined in the control (33.26 ng/mL), while the lowest was in FQV3 (27.75 ng/mL). The highest lysozyme activity was observed in FQV1 (154.64 U/mL), and the lowest in FQV2 (104.39 U/mL) and control (121.37 U/mL) (p < 0.05). FQV2 was characterized by significantly more favorable values of breeding indicators (p < 0.05). Conclusions: The obtained results prove that an appropriate composition of NaB, βG and vitamins can be used in the commercial breeding of juvenile hybrid sturgeons.
Unveiling the Mechanism of Compound Ku-Shen Injection in Liver Cancer Treatment through an Ingredient–Target Network Analysis
Authors: Zou Wenkui , Liu Jiazhen , Wei Zexing , Peng Chunhua , Zhao Ying , Ding Yue , Shi Jifan , Zhao Juan
Published: September 2024

Background: Compound Ku-Shen Injection (CKI) is a traditional Chinese medicine preparation derived from Ku-Shen and Bai-Tu-Ling, commonly used in the adjunctive treatment of advanced cancers, including liver cancer. However, the underlying mechanisms of CKI’s effectiveness in cancer treatment are not well defined. Methods: This study employs network pharmacology to investigate the traditional Chinese medicine (TCM) compatibility theory underlying CKI’s action in treating liver cancer, with findings substantiated by molecular docking and in vitro experiments. Sixteen active components were identified from CKI, along with 193 potential targets for treating liver cancer. Key therapeutic target proteins, including EGFR and ESR1, were also identified. KEGG enrichment results showed that the neuroactive ligand–receptor interaction, cAMP signaling pathway, and serotonergic synapses make up the key pathway of CKI in the treatment of liver cancer. Molecular docking results confirmed that the key active ingredients effectively bind to the core targets. CCK-8 cytotoxic experiment results show that the CKI key components of oxymatrine and matrine can inhibit the growth of HepG2 liver cancer cell proliferation. A Western blot analysis revealed that oxymatrine suppresses the expression of EGFR, contributing to its therapeutic efficacy against liver cancer. Conclusion: our study elucidated the therapeutic mechanism of CKI in treating liver cancer and unveiled the underlying principles of its TCM compatibility through its mode of action.
Patient-Reported Outcomes of Depression and Fibromyalgia Symptoms Do Not Predict Non-Inflammatory versus Inflammatory Diagnoses at Initial Rheumatology Consultation
Authors: Schäfer Arne , Kovacs Magdolna Szilvia , Nigg Axel , Feuchtenberger Martin
Published: September 2024

Objective: The objective of this study was to assess the potential value of patient-reported outcomes (PROs) of depression, fibromyalgia symptoms, and pain in predicting non-inflammatory vs. inflammatory diagnoses in rheumatology patients. Methods: This retrospective, single-center study evaluated electronic health record (EHR) data from adults who were seen for their first rheumatology consultation and subsequently received a diagnosis of an inflammatory (e.g., rheumatoid arthritis or spondyloarthritis) or non-inflammatory (e.g., osteoarthritis or fibromyalgia) condition. The PROs evaluated included depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]), fibromyalgia symptom severity (FM SS), and pain. Results: A total of 3669 patients were evaluated, including patients with (n = 984; 26.82%) and without (n = 2685; 73.18%) inflammatory rheumatologic disease, of whom 141 (3.8%) had fibromyalgia. The non-inflammatory subgroup reported higher FM SS scores, and the inflammatory subgroup had higher pain and inflammatory markers. Bivariate models based on PHQ-2 and FM SS had a very low specificity (0.3%) for predicting non-inflammatory conditions, resulting in the misclassification of >99% of inflammatory cases. Adding pain, inflammatory markers, and other relevant EHR variables increased specificity but still resulted in a high level of misclassification. Conclusions: The PROs evaluated in this study are not suitable for predicting non-inflammatory vs. inflammatory rheumatologic disease, even when combined with other EHR variables.
In Search of New Dimensions for Religious Tourism: The Case of the Ancient City of Nessebar
Authors: Mileva Sonia , Krachanova Milena
Published: September 2024

Religious tourism is a growing phenomenon that is increasingly intertwined with cultural tourism, particularly in countries like Bulgaria, which possesses a wealthy heritage of religious interest. The Ancient City of Nessebar, a UNESCO World Heritage site with a rich religious history, provides a unique case study for examining this dynamic. This study employed a mixed-methods approach, including documentary analysis and case study methodology, to investigate the current state of religious tourism in Nessebar. The research revealed the underutilization of Nessebar’s religious sites for tourism purposes, despite their potential value. A complex interplay between mass tourism, cultural preservation, and the decline of traditional religious practices was identified.
Revisiting Factors Influencing Under-Five Mortality in India: The Application of a Generalised Additive Cox Proportional Hazards Model
Authors: Khan Maroof Ahmad , Das Sumit Kumar
Published: September 2024

Background: Despite the implementation of various preventive measures, India continues to experience an alarmingly high under-five mortality rate (U5MR). The most recent nationwide data on U5MRs has provided an opportunity to re-examine the associated factors of U5MRs using advanced techniques. This study attempted to identify the associated determinants of U5MRs via the generalised additive Cox proportional hazards method. Methods: This study analysed the fifth round of unit-level data for 213,612 children from the National Family Health Survey (NFHS-5) to identify the risk factors associated with U5MRs, employing a generalised additive Cox proportional hazards regression analysis. Results: The children who had a length of pregnancy of less than 9 months had a 2.621 (95% CI: 2.494, 2.755) times greater hazard of U5MRs than the children who had a gestational period of 9 months or more. The non-linear association with U5MRs was highest in the mother’s age, followed by the mother’s haemoglobin, the mother’s education, and household wealth score. The relationships between the mother’s age and the mother’s haemoglobin level with the U5MR were found to be U-shaped. Conclusions: This study highlights the importance of addressing maternal and socioeconomic factors while improving access to healthcare services in order to reduce U5MRs in India. Furthermore, the findings underscore the necessity for more sophisticated approaches to healthcare delivery that consider the non-linear relationships between predictor variables and U5MRs.
Methods for a Non-Targeted Qualitative Analysis and Quantification of Benzene, Toluene, and Xylenes by Gas Chromatography-Mass Spectrometry of E-Liquids and Aerosols in Commercially Available Electronic Cigarettes in Mexico
Authors: Svarch-Pérez Alejandro , Paz-González María Vanessa , Ruiz-Juárez Carlota , Olvera-Chacón Juan C. , Larios-Solís Angelina , Castro-Gaytán Santiago , Aldeco-Pérez Eugenia , Alcocer-Varela Jorge Carlos
Published: September 2024

The chemical components of the e-liquids and aerosols contained in electronic nicotine delivery systems (ENDSs), better known as vapes, were evaluated. The analytical technique used was gas chromatography–mass spectrometry, where the extraction and injection methods were established in this study. The work consisted of the analysis of twenty samples of disposable electronic cigarettes prefilled with new e-liquid, of a known brand, flavor, volume, and, in some of them, the percentage of nicotine and the number of puffs per device were indicated on the label. We detected the presence of many substances (at a qualitative and semi-quantitative level), and we achieved the quantification of benzene, toluene, and xylenes (BTX), dangerous substances that cause severe damage to health. Several of the e-liquids and aerosols present BTX concentrations above the permissible exposure limit (PEL), recommended by the Occupational Safety and Health Administration (OSHA): benzene in aerosol samples 80% > PEL, and toluene in aerosol samples 45% > PEL. The number of chemical compounds found in the samples increases from 13 to 167, the average being 52 compounds for the water extraction method, 42 compounds for the methanol extraction method of e-liquids, and 107 compounds for the direct aerosol analysis. It is a fact that many of those compounds, especially BTX, can cause serious effects on human health, affecting the respiratory, digestive, cardiovascular, pulmonary, and immune systems, as well as the brain. Therefore, the use of these devices should be considered with caution, since the substances and their chemical nature may pose significant health risks to both users and those exposed to secondhand emissions.
In Vitro Profiling of the Antiviral Peptide TAT-I24
Authors: Ziu Theodhora , Sambur Ezgi , Ruzsics Zsolt , Hengel Hartmut , Grabherr Reingard , Höfinger Siegfried , Harant Hanna
Published: September 2024

The synthetic peptide TAT-I24 (GRKKRRQRRRPPQCLAFYACFC) exerts antiviral activity against several double-stranded (ds) DNA viruses, including herpes simplex viruses, cytomegalovirus, some adenoviruses, vaccinia virus and SV40 polyomavirus. In the present study, in vitro profiling of this peptide was performed with the aim of characterizing and improving its properties for further development. As TAT-I24 contains three free cysteine residues, a potential disadvantageous feature, peptide variants with replacements or deletions of specific residues were generated and tested in various cell systems and by biochemical analyses. Some cysteine replacements had no impact on the antiviral activity, such as the deletion of cysteine 14, which also showed improved biochemical properties, while the cyclization of cysteines 14 and 20 had the most detrimental effect on antiviral activity. At concentrations below 20 µM, TAT-I24 and selected variants did not induce hemolysis in red blood cells (RBCs) nor modulated lipopolysaccharide (LPS)-induced release of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), in human peripheral blood mononuclear cells (PBMCs). These data indicate that TAT-I24 or its peptide variants are not expected to cause unwanted effects on blood cells.
Biased Signaling Agonists Promote Distinct Phosphorylation and Conformational States of the Dopamine D3 Receptor
Authors: Nepal Binod , Barnett Jessica , Bearoff Frank , Kortagere Sandhya
Published: September 2024

Biased agonists of G-protein-coupled receptors (GPCRs) have emerged as promising selective modulators of signaling pathways by offering therapeutic advantages over unbiased agonists to minimize side effects. The dopamine D3 receptor (D3R), a pivotal GPCR in the central nervous system, has gained significant attention as a therapeutic target for neurological diseases, including Parkinson’s disease (PD), addiction, psychosis, depression, and anxiety. We have recently designed and tested SK609, a G-protein biased D3R selective agonist, and demonstrated its efficacy in reducing motor impairment and improving cognitive effects in a rodent model of PD. The molecular mechanism by which SK609 recruits G-protein but not β-arrestin pathways is poorly understood. Utilizing all-atom molecular dynamics simulations, we investigated the distinct conformational dynamics imparted by SK609 and the reference unbiased agonist Pramipexole (PRX). Results from these studies show that the flexibility of transmembrane 3 is key to unbiased signaling, with a ~30° and ~17° shift in tilt angle in the D3R-Gi and D3R-βarrestin2 complexes, respectively. Additionally, untargeted phosphoproteomics analysis reveals unique phosphorylation sites by SK609 and PRX in D3R. These results suggest that SK609 induces conformational changes and unique phosphorylation patterns that promote interactions with G-proteins and are not conducive for β-arrestin2 recruitment and signaling.
Methodological Approaches to Experimental Evaluation of Neuroprotective Action of Potential Drugs
Authors: Belenichev Igor , Bukhtiyarova Nina , Ryzhenko Victor , Makyeyeva Lyudmyla , Morozova Oksana , Oksenych Valentyn , Kamyshnyi Oleksandr
Published: September 2024

The authors propose a novel approach to a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while saving animal life by reducing the number of animals used in research. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable the assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate–calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity; signs of neurological deficits (paresis, paralysis, etc.); as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.
Surfactant Phospholipid Kinetics in Ventilated Children after Therapeutic Surfactant Supplementation
Authors: Goss Victoria M. , Dushianthan Ahilanandan , McCorkell Jenni , Morton Katy , Goss Kevin C. W. , Marsh Michael J. , Pappachan John V. , Postle Anthony D.
Published: September 2024

Acute lung Injury leads to alterations in surfactant lipid composition and metabolism. Although several mechanisms contribute to dysregulated surfactant metabolism, studies investigating in vivo surfactant metabolism are limited. The aim of this study is to characterise surfactant phospholipid composition and flux utilising a stable isotope labelling technique in mechanically ventilated paediatric patients. Paediatric patients (<16 years of age) received 3.6 mg/kg intravenous methyl-D9-choline chloride followed by the endotracheal instillation of 100 mg/kg of exogenous surfactant after 24 h. Bronchioalveolar fluid samples were taken at baseline and 12, 24, 36, 48, 72 and 96 h after methyl-D9-choline infusion. Nine participants (median age of 48 days) were recruited. The primary phosphatidylcholine (PC) composition consisted of PC16:0/16:0 or DPPC (32.0 ± 4.5%). Surfactant supplementation resulted in a 30% increase in DPPC. Methyl-D9 PC enrichment was detected after 12 h and differed significantly between patients, suggesting variability in surfactant synthesis/secretion by the CDP-choline pathway. Peak enrichment was achieved (0.94 ± 0.15% of total PC) at 24 h after methyl-D9-choline infusion. There was a trend towards reduced enrichment with the duration of mechanical ventilation prior to study recruitment; however, this was not statistically significant (p = 0.19). In this study, we demonstrated the fractional molecular composition and turnover of surfactant phospholipids, which was highly variable between patients.
Biallelic Loss of 7q34 (TRB) and 9p21.3 (CDKN2A/2B) in Adult Ph-Negative Acute T-Lymphoblastic Leukemia
Authors: Risinskaya Natalya , Abdulpatakhov Abdulpatakh , Chabaeva Yulia , Aleshina Olga , Gladysheva Maria , Nikulina Elena , Bolshakov Ivan , Yushkova Anna , Dubova Olga , Vasileva Anastasia , Obukhova Tatiana , Julhakyan Hunan , Kapranov Nikolay , Galtseva Irina , Kulikov Sergey , Sudarikov Andrey , Parovichnikova Elena
Published: September 2024

Tumor cells of acute lymphoblastic leukemia (ALL) may have various genetic abnormalities. Some of them lead to a complete loss of certain genes. Our aim was to reveal biallelic deletions of genes in Ph–negative T-ALL. Chromosomal microarray analysis (CMA) was performed for 47 patients with de novo Ph–negative T-ALL, who received treatment according to RALL-2016m clinical protocol at the National Medical Research Center for Hematology (Moscow, Russia) from 2017 to 2023. Out of forty-seven patients, only three had normal molecular karyotype. The other 44 patients had multiple gains, losses, and copy neutral losses of heterozygosity. Biallelic losses were found in 14 patients (30%). In ten patients (21%), a biallelic deletion of 9p21.3 involved a different number of genes, however CDKN2A gene loss was noted in all ten cases. For seven patients (15%), a biallelic deletion of 7q34 was found, including two genes—PRSS1, PRSS2 located within the T-cell receptor beta (TRB) locus. A clonal rearrangement of the TRB gene was revealed in 6 out of 7 cases with 7q34 biallelic loss. Both biallelic deletions can be considered favorable prognostic factors, with an association with 9p21 being statistically significant (p = 0.01) and a trend for 7q34 (p = 0.12) being observed.
Biology of Healthy Aging: Biological Hallmarks of Stress Resistance Related and Unrelated to Longevity in Humans
Authors: Badial Komalpreet , Lacayo Patricia , Murakami Shin
Published: September 2024

Stress resistance is highly associated with longer and healthier lifespans in various model organisms, including nematodes, fruit flies, and mice. However, we lack a complete understanding of stress resistance in humans; therefore, we investigated how stress resistance and longevity are interlinked in humans. Using more than 180 databases, we identified 541 human genes associated with stress resistance. The curated gene set is highly enriched with genes involved in the cellular response to stress. The Reactome analysis identified 398 biological pathways, narrowed down to 172 pathways using a medium threshold (p-value < 1 × 10−4). We further summarized these pathways into 14 pathway categories, e.g., cellular response to stimuli/stress, DNA repair, gene expression, and immune system. There were overlapping categories between stress resistance and longevity, including gene expression, signal transduction, immune system, and cellular responses to stimuli/stress. The categories include the PIP3-AKT-FOXO and mTOR pathways, known to specify lifespans in the model systems. They also include the accelerated aging syndrome genes (WRN and HGPS/LMNA), while the genes were also involved in non-overlapped categories. Notably, nuclear pore proteins are enriched among the stress-resistance pathways and overlap with diverse metabolic pathways. This study fills the knowledge gap in humans, suggesting that stress resistance is closely linked to longevity pathways but not entirely identical. While most longevity categories intersect with stress-resistance categories, some do not, particularly those related to cell proliferation and beta-cell development. We also note inconsistencies in pathway terminologies with aging hallmarks reported previously, and propose them to be more unified and integral.
Novel Oncogenic Value of C10orf90 in Colon Cancer Identified as a Clinical Diagnostic and Prognostic Marker
Authors: Ruan Chuangdong , Zhang Yuqin , Chen Daoyang , Zhu Mengyi , Yang Penghui , Zhang Rongxin , Li Yan
Published: September 2024

C10orf90, a tumor suppressor, can inhibit the occurrence and development of tumors. Therefore, we investigated the gene function of C10orf90 in various tumors using multiple pan-cancer datasets. Pan-cancer analysis results reveal that the expression levels of C10orf90 vary across different tumors and hold significant value in the clinical diagnosis and prognosis of patients with various tumors. In some cancers, the expression level of C10orf90 is correlated with CNV, DNA methylation, immune subtypes, immune cell infiltration, and drug sensitivity in the tumors. In particular, in COAD, the C10orf90 gene is implicated in multiple processes associated with COAD. Cell experiments demonstrate that C10orf90 suppresses the proliferation and migration of colon cancer cells while promoting apoptosis. In summary, C10orf90 plays a role in the onset and progression of various cancers and could potentially serve as an effective diagnostic and prognostic marker for cancer patients. Notably, in COAD, C10orf90 inhibits the proliferation and migration of colon cancer cells, induces apoptosis, and is linked to the advancement of colon cancer.
Monogenic Defects of Beta Cell Function: From Clinical Suspicion to Genetic Diagnosis and Management of Rare Types of Diabetes
Authors: Serbis Anastasios , Kantza Evanthia , Siomou Ekaterini , Galli-Tsinopoulou Assimina , Kanaka-Gantenbein Christina , Tigas Stelios
Published: September 2024

Monogenic defects of beta cell function refer to a group of rare disorders that are characterized by early-onset diabetes mellitus due to a single gene mutation affecting insulin secretion. It accounts for up to 5% of all pediatric diabetes cases and includes transient or permanent neonatal diabetes, maturity-onset diabetes of the young (MODY), and various syndromes associated with diabetes. Causative mutations have been identified in genes regulating the development or function of the pancreatic beta cells responsible for normal insulin production and/or release. To date, more than 40 monogenic diabetes subtypes have been described, with those caused by mutations in HNF1A and GCK genes being the most prevalent. Despite being caused by a single gene mutation, each type of monogenic diabetes, especially MODY, can appear with various clinical phenotypes, even among members of the same family. This clinical heterogeneity, its rarity, and the fact that it shares some features with more common types of diabetes, can make the clinical diagnosis of monogenic diabetes rather challenging. Indeed, several cases of MODY or syndromic diabetes are accurately diagnosed in adulthood, after having been mislabeled as type 1 or type 2 diabetes. The recent widespread use of more reliable sequencing techniques has improved monogenic diabetes diagnosis, which is important to guide appropriate treatment and genetic counselling. The current review aims to summarize the latest knowledge on the clinical presentation, genetic confirmation, and therapeutic approach of the various forms of monogenic defects of beta cell function, using three imaginary clinical scenarios and highlighting clinical and laboratory features that can guide the clinician in reaching the correct diagnosis.
Peroxymonosulfate Activation by Fe@N Co-Doped Biochar for the Degradation of Sulfamethoxazole: The Key Role of Pyrrolic N
Authors: Liu Tong , Li Chenxuan , Chen Xing , Chen Yihan , Cui Kangping , Wang Dejin , Wei Qiang
Published: September 2024

In this study, Fe, N co-doped biochar (Fe@N co-doped BC) was synthesized by the carbonization–pyrolysis method and used as a carbocatalyst to activate peroxymonosulfate (PMS) for sulfamethoxazole (SMX) removal. In the Fe@N co-doped BC/PMS system, the degradation efficiency of SMX (10.0 mg·L−1) was 90.2% within 40 min under optimal conditions. Radical quenching experiments and electron spin resonance (ESR) analysis suggested that sulfate radicals (SO4•−), hydroxyl radicals (•OH), and singlet oxygen (1O2) participated in the degradation process. After the reaction, the proportion of pyrrolic N decreased from 57.9% to 27.1%. Pyrrolic N served as an active site to break the inert carbon network structure and promote the generation of reactive oxygen species (ROS). In addition, pyrrolic N showed a stronger interaction with PMS and significantly reduced the activation energy required for the reaction (∆G = 23.54 kcal/mol). The utilization potentiality of Fe@N co-doped BC was systematically evaluated in terms of its reusability and selectivity to organics. Finally, the intermediates of SMX were also detected.
IFN Lambda Deficiency Contributes to Severe COVID-19 Outcomes
Authors: Zaleska Anna , Dor-Wojnarowska Anna , Radlińska Anna , Rorat Marta , Szymański Wojciech , Gajewski Adrian , Chałubiński Maciej
Published: September 2024

Interferons (IFNs) produced by airway epithelial cells are crucial in defending against pathogens. Fluctuations in IFN-λ levels may influence coronavirus disease 19 (COVID-19) severity. However, conflicting data have been reported regarding serum IFN-λ concentrations in COVID-19 patients. To address this, we evaluated serum IFN-λ levels over time in moderate and severe COVID-19 patients and their association with cytokine production and clinical parameters using the enzyme-linked immunosorbent assay (ELISA) and the Bio-Plex Pro Human Cytokine 17-plex Assay. Results from testing 51 COVID-19 patients showed that 68% lacked detectable serum IFN-λ. Among non-IFN-λ secretors, severe COVID-19 predominated. In contrast, IFN-λ secretors displayed stable IFN-λ levels in moderate cases, while severe cases showed a decline over time, which persisted even after recovery. A negative correlation was observed between IFN-λ levels and inflammatory markers. This, combined with an increase in tumor necrosis factor alpha (TNF-α) and clinical improvement, suggests a regulatory role for IFN-λ in promoting faster recovery. Despite this, survival rates were similar between the groups, indicating that while IFN-λ influences the course of the disease, it does not directly affect overall survival. In conclusion, IFN-λ is vital, but not unique, for the antiviral response and COVID-19 recovery. Simultaneously, serum IFN-λ deficiency signifies severe COVID-19.
Analysis of Punicalin and Punicalagin Interaction with PDIA3 and PDIA1
Authors: Meschiari Giorgia , Minacori Marco , Fiorini Sara , Tedesco Mariassunta , Eufemi Margherita , Altieri Fabio
Published: September 2024

PDIA3 is a pleiotropic protein primarily located in the endoplasmic reticulum where it is involved in protein folding, catalyzing the formation, breakage, and rearrangement of disulfide bonds. PDIA3 is implicated in numerous pathologies such as cancer, inflammation, and neurodegeneration. Although punicalagin has been proven to be a highly promising PDIA3 inhibitor and can be used as target protein in glioblastoma, it does not have sufficient selectivity for PDIA3 and is a quite-large molecule. With the aim of finding punicalagin derivatives with a simplified structure, we selected punicalin, which lacks the hexahydroxy-diphenic acid moiety. Previous docking studies suggest that this part of the molecule is not involved in the binding with PDIA3. In this study we compared the ability of punicalin to bind and inhibit PDIA3 and PDIA1. Tryptophan fluorescence quenching and disulfide reductase activity (using both glutathione and insulin as substrates) were evaluated, demonstrating the ability of punicalin to bind and inhibit PDIA3 even to a lesser extent compared to punicalagin. On the other hand, punicalin showed a very low inhibition activity towards PDIA1, demonstrating a higher selectivity for PDIA3. Protein thermal shift assay evidenced that both proteins can be destabilized by punicalin as well as punicalagin, with PDIA3 much more sensitive. Additionally, punicalin showed a higher change in the thermal stability of PDIA3, with a shift up to 8 °C. This result could explain the presence of PDIA3 aggregates, evidenced by immunofluorescence analysis, that accumulate within treated cells and that are more evident in the presence of punicalin. The results here obtained show punicalin is able to bind both proteins but with a higher selectivity for PDIA3, suggesting the possibility of developing new molecules with a simplified structure that are still able to selectively bind and inhibit PDIA3.
Circulating Matrix Metalloproteinases for Prediction of Aortic Dilatation in Children with Bicuspid Aortic Valve: A Single-Center, Observational Study
Authors: Făgărășan Amalia , Săsăran Maria Oana , Gozar Liliana , Toma Daniela , Șuteu Carmen , Ghiragosian-Rusu Simina , Al-Akel Flavia Cristina , Szabo Boglarka , Huțanu Adina
Published: September 2024

Circulating biomarkers have been proposed for early identification of aortic dilatation progression associated with bicuspid aortic valve (BAV), but matrix metalloproteinases (MMPs) are distinguished as signatures of increased extracellular matrix degradation, a landmark of aneurysm formation. The current study aims to identify the role of MMP-1, MMP-2, MMP-9, and the MMP inhibitor, TIMP-1, in identifying aortic dilation in children with BAV. We conducted a study on 73 children divided into two study groups, depending on the presence of aortic dilatation (group 1–43 BAV controls and group 2–30 children with BAV and aortic dilatation). Each patient underwent a cardiac ultrasound and, in each case, serum MMP-1, MMP-2, MMP-9, and TIMP-1 were quantified using xMAP technology. Comparison of the MMPs between the two study groups revealed significantly higher values only in the case of TIMP-1, among BAV controls. Moreover, the same TIMP-1 inversely correlated with aortic annulus absolute size and z score, as well as with ascending aorta z score. No particular correlation between the aortic phenotype and the presence of aortic dilatation was found. Future longitudinal research starting at pediatric ages could show the significance of MMPs screening in BAV individuals as predictors of aortic aneurysm formation.
RMD and Its Suppressor MAPK6 Control Root Circumnutation and Obstacle Avoidance via BR Signaling
Authors: Dong Le , Shi Jianxin , Persson Staffan , Huang Guoqiang , Zhang Dabing
Published: September 2024

Helical growth of the root tip (circumnutation) that permits surface exploration facilitates root penetration into soil. Here, we reveal that rice actin-binding protein RMD aids in root circumnutation, manifested by wavy roots as well as compromised ability to efficiently explore and avoid obstacles in rmd mutants. We demonstrate that root circumnutation defects in rmd depend on brassinosteroid (BR) signaling, which is elevated in mutant roots. Suppressing BR signaling via pharmacological (BR inhibitor) or genetic (knockout of BR biosynthetic or signaling components) manipulation rescues root defects in rmd. We further reveal that mutations in MAPK6 suppress BR signaling and restore normal root circumnutation in rmd, which may be mediated by the interaction between MAPK6, MAPKK4 and BR signaling factor BIM2. Our study thus demonstrates that RMD and MAPK6 control root circumnutation by modulating BR signaling to facilitate early root growth.
Could the Adoptive Transfer of Memory Lymphocytes be an Alternative Treatment for Acinetobacter baumannii Infections?
Authors: Cebrero-Cangueiro Tania , Herrera-Espejo Soraya , Paniagua María , Labrador-Herrera Gema , Cisneros José Miguel , Pachón Jerónimo , Pachón-Ibáñez María Eugenia
Published: September 2024

We evaluated the efficacy of the adoptive transfer of memory B, CD4+, and CD8+ T lymphocytes compared with sulbactam and tigecycline in an experimental murine pneumonia model by two multidrug-resistant Acinetobacter baumannii strains, colistin-susceptible AbCS01 and colistin-resistant AbCR17. Pharmacodynamically optimized antimicrobial dosages were administered for 72 h, and intravenous administration of 2 × 106 of each of the memory cells in a single dose 30 min post-infection. Bacterial lung and blood counts and mortality rates were analyzed. Results showed that a single dose of memory B or CD4+ T cells was as effective as sulbactam in terms of bacterial clearance from the lungs and blood compared with the untreated mice or the tigecycline-treated mice inoculated with the AbCS01 strain. In the pneumonia model by AbCR17, a single dose of memory B or CD4+ T cells also reduced the bacterial load in the lungs compared with both antibiotic groups and was more efficacious than tigecycline in terms of blood clearance. Regarding survival, the adoptive transfer of memory B or CD4+ T cells was as effective as three days of sulbactam treatment for both strains. These data suggest that adoptive memory cell transfer could be a new effective treatment of multidrug-resistant A. baumannii infections.
TRPV4 Channel Modulators as Potential Drug Candidates for Cystic Fibrosis
Authors: Orfali Razan , AlFaiz Ali , Alanazi Madhawi , Alabdulsalam Rahaf , Alharbi Meaad , Alromaih Yara , Dallak Ismail , Alrahal Marah , Alwatban Abdulaziz , Saud Reem
Published: September 2024

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective chloride ion channels. This leads to thick, dehydrated mucus that severely disrupts mucociliary clearance in the respiratory system and triggers infection that eventually is the cause of death of CF patients. Current therapeutic strategies primarily focus on restoring CFTR function, blocking epithelial sodium channels to prevent mucus dehydration, or directly targeting mucus to reduce its viscosity. Among the ion channels expressed in ciliated bronchial epithelial cells, the transient receptor potential vanilloid 4 (TRPV4) channel emerges as a significant channel in CF pathogenesis. Activation of TRPV4 channels affects the regulation of airway surface liquid by modulating sodium absorption and intracellular calcium levels, which indirectly influences CFTR activity. TRPV4 is also involved in the regulatory volume decrease (RVD) process and enhances inflammatory responses in CF patients. Here, we combine current findings on TRPV4 channel modulation as a promising therapeutic approach for CF. Although limited studies have directly explored TRPV4 in CF, emerging evidence indicates that TRPV4 activation can significantly impact key pathological processes in the disease. Further investigation into TRPV4 modulators could lead to innovative treatments that alleviate severe respiratory complications and improve outcomes for CF patients.
Novel Insight into the Prevention and Therapeutic Treatment of Paulownia Witches’ Broom: A Study on the Effect of Salicylic Acid on Disease Control and the Changes in the Paulownia Transcriptome and Proteome
Authors: Fan Yujie , Zhu Peipei , Zhao Hui , Yang Haibo , Wang Wenhu , Fan Guoqiang
Published: September 2024

Paulownia species not only have significant economic benefits but also show great potential in ecological conservation. However, they are highly susceptible to phytoplasma infections, causing Paulownia witches’ broom (PaWB), which severely restricts the development of the Paulownia industry. Salicylic acid (SA) plays a crucial role in plant disease resistance. However, there have been no reports on the effect of SA on PaWB. Due to the properties of SA, it may have potential in controlling PaWB. Based on the above speculation, the prevention and therapeutic effect of SA on PaWB and its effect on the PaWB-infected Paulownia transcriptome and proteome were studied in this work. The results indicated that 0.1 mmol/L was the optimal SA concentration for inhibiting the germination of Paulownia axillary buds. In terms of resistance physiological indicators, SA treatment significantly affected both Paulownia tomentosa infected (PTI) seedlings and Paulownia fortunei infected (PFI) seedlings, where the activities of peroxidase (POD) and superoxide dismutase (SOD) were enhanced. Malondialdehyde (MDA), O2−, and H2O2, however, were significantly reduced. Specifically, after SA treatment, SOD activity increased by 28% in PFI and 25% in PTI, and POD activity significantly increased by 61% in PFI and 58% in PTI. Moreover, the MDA content decreased by 30% in PFI and 23% in PTI, the H2O2 content decreased by 26% in PFI and 19% in PTI, and the O2− content decreased by 21% in PFI and 19% in PTI. Transcriptomic analysis showed that there were significant upregulations of MYB, NAC, and bHLH and other transcription factors after SA treatment. Moreover, genes involved in PaWB-related defense responses such as RAX2 also showed significant differences. Furthermore, proteomic analysis indicated that after SA treatment, proteins involved in signal transduction, protein synthesis modification, and disease defense were differentially expressed. This work provides a research foundation for the prevention and treatment of PaWB and offers references for exploring anti-PaWB methods.
Identification of Genomic Regions Conferring Enhanced Zn and Fe Concentration in Wheat Varieties and Introgression Lines Derived from Wild Relatives
Authors: Leonova Irina N. , Kiseleva Antonina A. , Salina Elena A.
Published: September 2024

Wild and cultivated relatives of wheat are an important source of genetic factors for improving the mineral composition of wheat. In this work, a wheat panel consisting of modern bread wheat varieties, landraces, and introgression lines with genetic material of the wheat species Triticum timopheevii, T. durum, T. dicoccum, and T. dicoccoides and the synthetic line T. kiharae was used to identify loci associated with the grain zinc (GZnC) and iron (GFeC) content. Using a BLINK model, we identified 31 and 73 marker–trait associations (MTAs) for GZnC and GFeC, respectively, of which 19 were novel. Twelve MTAs distributed on chromosomes 1B, 2A, 2B, 5A, and 5B were significantly associated with GZnC, five MTAs on 2A, 2B, and 5D chromosomes were significantly associated with GFeC, and two SNPs located on 2A and 2B were related to the grain concentration of both trace elements. Meanwhile, most of these MTAs were inherited from At and G genomes of T. timopheevii and T. kiharae and positively affected GZnC and GFeC. Eight genes related to iron or zinc transporters, representing diverse gene families, were proposed as the best candidates. Our findings provide an understanding of the genetic basis of grain Zn and Fe accumulation in species of the Timopheevi group and could help in selecting new genotypes containing valuable loci.
A Customizable Platform to Integrate CAR and Conditional Expression of Immunotherapeutics in T Cells
Authors: Nguyen Huong T. X. , Song Yabin , Kumar Satendra , Liang Fu-Sen
Published: September 2024

The potential of chimeric antigen receptor (CAR)-based immunotherapy as a promising therapeutic approach is often hindered by the presence of highly immunosuppressive tumor microenvironments (TME). Combination therapies with either co-administration or built-in expression of additional TME-modulating therapeutic molecules to potentiate the functions of CAR-T cells can cause systemic toxicities due to the lack of control over the delivery of biologics. Here, we present a proof-of-concept engineered platform in human Jurkat T cells that combines CAR with a therapeutic gene circuit capable of sensing β-galactosidase (a reported cancer-associated signal) and subsequently activate the production of customized therapeutic gene products. We have demonstrated the integration of the chemically induced proximity (CIP) and associated signal sensing technologies with CAR in this study. A β-galactosidase-activatable prodrug was designed by conjugating a galactose moiety with a CIP inducer abscisic acid (ABA). We showed that Jurkat T cells engineered with CAR and the ABA-inducible genetic circuits can respond to recombinant β-galactosidase to drive the production and secretion of various immunotherapeutics including an anti-cancer agent, an immunomodulatory cytokine, and immune checkpoint inhibitors. Our design is highly modular and could be adapted to sense different cancer-related signals to locally produce antitumor therapeutics that can potentially boost CAR-T efficacy and persistence.
Review of Novel Surgical, Radiation, and Systemic Therapies and Clinical Trials in Glioblastoma
Authors: Valerius Allison R. , Webb Lauren M. , Thomsen Anna , Lehrer Eric J. , Breen William G. , Campian Jian L. , Riviere-Cazaux Cecile , Burns Terry C. , Sener Ugur
Published: September 2024

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite an established standard of care including surgical resection, radiation therapy, and chemotherapy, GBM unfortunately is associated with a dismal prognosis. Therefore, researchers are extensively evaluating avenues to expand GBM therapy and improve outcomes in patients with GBM. In this review, we provide a broad overview of novel GBM therapies that have recently completed or are actively undergoing study in clinical trials. These therapies expand across medical, surgical, and radiation clinical trials. We additionally review methods for improving clinical trial design in GBM.
Edge Computing and Cloud Computing for Internet of Things: A Review
Authors: Andriulo Francesco Cosimo , Fiore Marco , Mongiello Marina , Traversa Emanuele , Zizzo Vera
Published: September 2024

The rapid expansion of the Internet of Things ecosystem has created an urgent need for efficient data processing and analysis technologies. This review aims to systematically examine and compare edge computing, cloud computing, and hybrid architectures, focusing on their applications within IoT environments. The methodology involved a comprehensive search and analysis of peer-reviewed journals, conference proceedings, and industry reports, highlighting recent advancements in computing technologies for IoT. Key findings reveal that edge computing excels in reducing latency and enhancing data privacy through localized processing, while cloud computing offers superior scalability and flexibility. Hybrid approaches, such as fog and mist computing, present a promising solution by combining the strengths of both edge and cloud systems. These hybrid models optimize bandwidth use and support low-latency, privacy-sensitive applications in IoT ecosystems. Hybrid architectures are identified as particularly effective for scenarios requiring efficient bandwidth management and low-latency processing. These models represent a significant step forward in addressing the limitations of both edge and cloud computing for IoT, offering a balanced approach to data analysis and resource management.
Integrated Iot Approaches for Crop Recommendation and Yield-Prediction Using Machine-Learning
Authors: Bouni Mohamed , Hssina Badr , Douzi Khadija , Douzi Samira
Published: September 2024

In this study, we present an integrated approach utilizing IoT data and machine learning models to enhance precision agriculture. We collected an extensive IoT secondary dataset from an online data repository, including environmental parameters such as temperature, humidity, and soil nutrient levels, from various sensors deployed in agricultural fields. This dataset, consisting of over 1 million data points, provided comprehensive insights into the environmental conditions affecting crop yield. The data were preprocessed and used to develop predictive models for crop yield and recommendations. Our evaluation shows that the LightGBM, Decision Tree, and Random Forest classifiers achieved high accuracy scores of 98.90%, 98.48%, and 99.31%, respectively. The IoT data collection enabled real-time monitoring and accurate data input, significantly improving the models’ performance. These findings demonstrate the potential of combining IoT and machine learning to optimize resource use and improve crop management in smart farming. Future work will focus on expanding the dataset to include more diverse environmental factors and exploring the integration of advanced deep learning techniques for even more accurate predictions.