bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban Internal Network Structure and Resilience Characteristics from the Perspective of Population Mobility: A Case Study of Nanjing, China
Authors: Li Zherui , Chen Wen , Liu Wei , Cui Zhe
Published: September 2024

In the face of diverse chronic pressures and increased factor mobility, the resilience of urban internal network structures has become a cutting-edge research topic. This study utilizes 2019 mobile signaling big data to construct employment and recreational flow networks among 101 townships and streets within Nanjing City. Based on the characteristics of these network structures, the resilience of the network structure is measured from the perspectives of density, symmetry, and transmissibility through interruption simulation techniques. The results show that the intensity of population mobility within Nanjing presents a general decay from the central urban area to the outer layers. In the employment scenario, cross-river population mobility is more frequent, while in the recreational scenario, the natural barrier effect of the Yangtze River is prominent. Due to the concentration of employment centers and high spatial heterogeneity, the employment flow network exhibits greater vulnerability to sudden shocks. Townships and streets with weighted degree values ranking around 60 and 80 are of great importance for maintaining the normal operation of both employment and recreational flow networks. Strengthening the construction of resilient parks and village planning within resilient cities can enhance the risk resistance of employment and recreational flow networks.
ETS Transcription Factors in Immune Cells and Immune-Related Diseases
Authors: Yang Yaxu , Han Xue , Sun Lijun , Shao Fangyu , Yin Yue , Zhang Weizhen
Published: September 2024

The development, differentiation, and function of immune cells are precisely regulated by transcription factors. The E26 transformation-specific (ETS) transcription factor family is involved in various physiological and pathological processes by regulating cell proliferation, differentiation, and apoptosis. Emerging evidence has suggested that ETS family proteins are intimately involved in the development and function of immune cells. This review summarizes the role of the ETS family in immune cells and immune-related disorders. Seven transcription factors within the ETS family, including PU.1, ETV5, ETV6, ETS1/2, ELK3, and ELF1, play essential roles in the development and function of T cells, B cells, macrophages, neutrophils, and dendritic cells. Furthermore, they are involved in the occurrence and development of immune-related diseases, including tumors, allergies, autoimmune diseases, and arteriosclerosis. This review is conducive to a comprehensive overview of the role of the ETS family in immune cells, and thus is informative for the development of novel therapeutic strategies targeting the ETS family for immune-related diseases.
Anti-Inflammatory Cytokine Profiles in Thrombotic Thrombocytopenic Purpura—Differences Compared to COVID-19
Authors: Demeter Flóra , Bihari György , Vadicsku Dorina , Sinkovits György , Kajdácsi Erika , Horváth Laura , Réti Marienn , Müller Veronika , Iványi Zsolt , Gál János , Gopcsa László , Reményi Péter , Szathmáry Beáta , Lakatos Botond , Szlávik János , Bobek Ilona , Prohászka Zita Z. , Förhécz Zsolt , Masszi Tamás , Vályi-Nagy István , Prohászka Zoltán , Cervenak László
Published: September 2024

Thromboinflammation/immunothrombosis plays a role in several diseases including thrombotic thrombocytopenic purpura (TTP) and COVID-19. Unlike the extensive research that has been conducted on COVID-19 cytokine storms, the baseline and acute phase cytokine profiles of TTP are poorly characterized. Moreover, we compared the cytokine profiles of TTP and COVID-19 to identify the disease-specific/general characteristics of thromboinflammation/immunothrombosis. Plasma concentrations of 33 soluble mediators (SMs: cytokines, chemokines, soluble receptors, and growth factors) were measured by multiplex bead-based LEGENDplex™ immunoassay from 32 COVID-19 patients (32 non-vaccinated patients in three severity groups), 32 TTP patients (remission/acute phase pairs of 16 patients), and 15 control samples. Mainly, the levels of innate immunity-related SMs changed in both diseases. In TTP, ten SMs decreased in both remission and acute phases compared to the control, one decreased, and two increased only in the acute phase compared to remission, indicating mostly anti-inflammatory changes. In COVID-19, ten pro-inflammatory SMs increased, whereas one decreased with increasing severity compared to the control. In severe COVID-19, sixteen SMs exceeded acute TTP levels, with only one higher in TTP. PCA identified CXCL10, IL-1RA, and VEGF as the main discriminators among their cytokine profiles. The innate immune response is altered in both diseases. The cytokine profile of TTP suggests a distinct pathomechanism from COVID-19 and supports referring to TTP as thromboinflammatory rather than immunothrombotic, emphasizing thrombosis over inflammation as the driving force of the acute phase.
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer: Current Use and Future Prospects
Authors: Dickerson Henry , Diab Ahmad , Al Musaimi Othman
Published: September 2024

Tyrosine kinase inhibitors (TKIs) have emerged as a leading targeted cancer therapy, reducing the side effects often seen with non-targeted treatments, especially the damage to healthy cells. To tackle resistance, typically caused by epidermal growth factor receptor (EGFR) mutations, four generations of TKIs have been developed. Each generation has shown improved effectiveness and fewer side effects, resulting in better patient outcomes. For example, patients on gefitinib, a first-generation TKI, experienced a progression-free survival (PFS) of 10 months compared to 5 months with conventional chemotherapy. Second-generation TKI afatinib outperformed erlotinib and extended PFS to 11.1 months compared to 6.9 months with cisplatin. Third-generation TKIs further increased survival to 38.6 months, compared to 31.8 months with first-generation TKIs. This progress demonstrates the ability of newer TKIs to overcome resistance, particularly the T790M mutation, while reducing adverse effects. Ongoing research focuses on overcoming resistance from newer mutations like C797S to further improve patient survival. These developments highlight the significant progress in TKI therapy and the continued effort to refine cancer treatment. Recent research in South Korea shows that third-generation TKIs are ineffective against non-small cell lung cancer (NSCLC) with the C797S mutation. Several trials have started showing promising in vitro and in vivo results, but more trials are needed before clinical approval. This review underscores notable advancements in the field of EGFR TKIs, offering a comprehensive analysis of their mechanisms of action and the progression of various TKI generations in response to resistance.
A New Approach for CRISPR/Cas9 Editing and Selection of Pathogen-Resistant Plant Cells of Wine Grape cv. ‘Merlot’
Authors: Fizikova Anastasia , Tukhuzheva Zhanneta , Zhokhova Lada , Tvorogova Varvara , Lutova Ludmila
Published: September 2024

Grape is one of the most economically significant berry crops. Owing to the biological characteristics of grapes, such as the long juvenile period (5–8 years), high degree of genome heterozygosity, and the frequent occurrence of inbreeding depression, homozygosity during crossbreeding leads to loss of varietal characteristics and viability. CRISPR/Cas editing has become the tool of choice for improving elite technical grape varieties. This study provides the first evidence of a decrease in the total fraction of phenolic compounds and an increase in the concentration of peroxide compounds in grape callus cells upon the addition of chitosan to the culture medium. These previously unreported metabolic features of the grape response to chitosan have been described and used for the first time to increase the probability of selecting plant cells with MLO7 knockout characterised by an oxidative burst in response to the presence of a pathogen modulated by chitosan in the high-metabolite black grape variety ‘Merlot’. This was achieved by using a CRISPR/Cas9 editing vector construction with the peroxide sensor HyPer as a reporter. This research represents the first CRISPR/Cas9 editing of ‘Merlot’, one of the most economically important elite technical grape varieties.
The Delayed Turnover of Proteasome Processing of Myocilin upon Dexamethasone Stimulation Introduces the Profiling of Trabecular Meshwork Cells’ Ubiquitylome
Authors: Tundo Grazia Raffaella , Cavaterra Dario , Pandino Irene , Zingale Gabriele Antonio , Giammaria Sara , Boccaccini Alessandra , Michelessi Manuele , Roberti Gloria , Tanga Lucia , Carnevale Carmela , Figus Michele , Grasso Giuseppe , Coletta Massimo , Bocedi Alessio , Oddone Francesco , Sbardella Diego
Published: September 2024

Glaucoma is chronic optic neuropathy whose pathogenesis has been associated with the altered metabolism of Trabecular Meshwork Cells, which is a cell type involved in the synthesis and remodeling of the trabecular meshwork, the main drainage pathway of the aqueous humor. Starting from previous findings supporting altered ubiquitin signaling, in this study, we investigated the ubiquitin-mediated turnover of myocilin (MYOC/TIGR gene), which is a glycoprotein with a recognized role in glaucoma pathogenesis, in a human Trabecular Meshwork strain cultivated in vitro in the presence of dexamethasone. This is a validated experimental model of steroid-induced glaucoma, and myocilin upregulation by glucocorticoids is a phenotypic marker of Trabecular Meshwork strains. Western blotting and native-gel electrophoresis first uncovered that, in the presence of dexamethasone, myocilin turnover by proteasome particles was slower than in the absence of the drug. Thereafter, co-immunoprecipitation, RT-PCR and gene-silencing studies identified STUB1/CHIP as a candidate E3-ligase of myocilin. In this regard, dexamethasone treatment was found to downregulate STUB1/CHIP levels by likely promoting its proteasome-mediated turnover. Hence, to strengthen the working hypothesis about global alterations of ubiquitin-signaling, the first profiling of TMCs ubiquitylome, in the presence and absence of dexamethasone, was here undertaken by diGLY proteomics. Application of this workflow effectively highlighted a robust dysregulation of key pathways (e.g., phospholipid signaling, β-catenin, cell cycle regulation) in dexamethasone-treated Trabecular Meshwork Cells, providing an ubiquitin-centered perspective around the effect of glucocorticoids on metabolism and glaucoma pathogenesis.
An 8-SNP LDL Cholesterol Polygenic Score: Associations with Cardiovascular Risk Traits, Familial Hypercholesterolemia Phenotype, and Premature Coronary Heart Disease in Central Romania
Authors: Mănescu Ion Bogdan , Gabor Manuela Rozalia , Moldovan George Valeriu , Hadadi László , Huțanu Adina , Bănescu Claudia , Dobreanu Minodora
Published: September 2024

Familial hypercholesterolemia (FH) is the most significant inherited risk factor for coronary heart disease (CHD). Current guidelines focus on monogenic FH, but the polygenic form is more common and less understood. This study aimed to assess the clinical utility of an 8-SNP LDLC polygenic score in a central Romanian cohort. The cohort included 97 healthy controls and 125 patients with premature (P)CHD. The weighted LDLC polygenic risk score (wPRS) was analyzed for associations with relevant phenotypic traits, PCHD risk, and clinical FH diagnosis. The wPRS positively correlated with LDLC and DLCN scores, and LDLC concentrations could be predicted by wPRS. A trend of increasing LDLC and DLCN scores with wPRS deciles was observed. A +1 SD increase in wPRS was associated with a 36% higher likelihood of having LDLC > 190 mg/dL and increases in LDLC (+0.20 SD), DLCN score (+0.16 SD), and BMI (+0.15 SD), as well as a decrease in HDLC (−0.14 SD). Although wPRS did not predict PCHD across the entire spectrum of values, individuals above the 90th percentile were three times more likely to have PCHD compared to those within the 10th or 20th percentiles. Additionally, wPRS > 45th percentile identified “definite” clinical FH (DLCN score > 8) with 100% sensitivity and 45% specificity. The LDLC polygenic score correlates with key phenotypic traits, and individuals with high scores are more likely to have PCHD. Implementing this genetic tool may enhance risk prediction and patient stratification. These findings, the first of their kind in Romania, are consistent with the existing literature.
Anti TNF-Alpha Treatment Improves Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients
Authors: Caraba Alexandru , Stancu Oana , Crișan Viorica , Georgescu Doina
Published: September 2024

Nailfold capillaroscopy is a non-invasive investigation, which allows for the study of the microvasculature (anatomical and functional). Rheumatoid arthritis (RA) is associated with a high risk of cardiovascular atherosclerotic diseases, with endothelial dysfunction (macrovascular and microvascular) representing the first step in atherosclerosis development. The aim of this study is represented by the assessment of microvascular endothelial dysfunction in RA patients by means of nailfold capillaroscopy and to assess its evolution after a period of 12 months of anti TNF-alpha treatment. The study included 70 consecutive patients with RA and 70 healthy subjects, matched for age and gender, as the control group. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were evaluated in all patients, but in controls, only rheumatoid factor, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were measured. The RA activity was measured by DAS28. Nailfold capillaroscopy was carried out in all patients and controls, determining the baseline nailfold capillary density (Db), nailfold capillary density during reactive hyperemia (Dh), and nailfold capillary density after venous congestion (Dc). Data were presented as mean ± standard deviation. Statistical analysis was performed using ANOVA and Pearson’s correlation, with p < 0.05 being statistically significant. Db, Dh, and Dc were lower in RA patients than in controls (p < 0.0001), correlating with RA activity and TNF-α (p < 0.05). After 12 months of anti TNF-α treatment, microvascular endothelial dysfunction improved (p < 0.0001). Microvascular endothelial dysfunction can be assessed by nailfold capillaroscopy, with anti TNF-α medication contributing to its improvement.
Effects of Bifidobacterium-Fermented Milk on Obesity: Improved Lipid Metabolism through Suppression of Lipogenesis and Enhanced Muscle Metabolism
Authors: Maruta Hitomi , Fujii Yusuke , Toyokawa Naoki , Nakamura Shoji , Yamashita Hiromi
Published: September 2024

Obesity is a major global health concern. Studies suggest that the gut microflora may play a role in protecting against obesity. Probiotics, including lactic acid bacteria and Bifidobacterium, have garnered attention for their potential in obesity prevention. However, the effects of Bifidobacterium-fermented products on obesity have not been thoroughly elucidated. Bifidobacterium, which exists in the gut of animals, is known to enhance lipid metabolism. During fermentation, it produces acetic acid, which has been reported to improve glucose tolerance and insulin resistance, and exhibit anti-obesity and anti-diabetic effects. Functional foods have been very popular around the world, and fermented milk is a good candidate for enrichment with probiotics. In this study, we aim to evaluate the beneficial effects of milks fermented with Bifidobacterium strains on energy metabolism and obesity prevention. Three Bifidobacterium strains (Bif-15, Bif-30, and Bif-39), isolated from newborn human feces, were assessed for their acetic acid production and viability in milk. These strains were used to ferment milk. Otsuka–Long–Evans Tokushima Fatty (OLETF) rats administered Bif-15-fermented milk showed significantly lower weight gain compared to those in the water group. The phosphorylation of AMPK was increased and the expression of lipogenic genes was suppressed in the liver of rats given Bif-15-fermented milk. Additionally, gene expression related to respiratory metabolism was significantly increased in the soleus muscle of rats given Bif-15-fermented milk. These findings suggest that milk fermented with the Bifidobacterium strain Bif-15 can improve lipid metabolism and suppress obesity.
Chlorogenic Acid Enhances the Intestinal Health of Weaned Piglets by Inhibiting the TLR4/NF-κB Pathway and Activating the Nrf2 Pathway
Authors: Zhang Beibei , Tian Min , Wu Jing , Qiu Yueqin , Xu Xiaoming , Tian Chaoyang , Hou Jing , Wang Li , Gao Kaiguo , Yang Xuefen , Jiang Zongyong
Published: September 2024

Chlorogenic acid (CGA) is a natural polyphenol with potent antioxidant and anti-inflammatory activities. However, the exact role of it in regulating intestinal health under oxidative stress is not fully understood. This study aims to investigate the effects of dietary CGA supplementation on the intestinal health of weaned piglets under oxidative stress, and to explore its regulatory mechanism. Twenty-four piglets were randomly divided into two groups and fed either a basal diet (CON) or a basal diet supplemented with 200 mg/kg CGA (CGA). CGA reduced the diarrhea rate, increased the villus height in the jejunum, and decreased the crypt depth in the duodenum, jejunum, and ileum of the weaned piglets (p < 0.05). Moreover, CGA increased the protein abundance of Claudin-1, Occludin, and zonula occludens (ZO)-1 in the jejunum and ileum (p < 0.05). In addition, CGA increased the mRNA expression of pBD2 in the jejunum, and pBD1 and pBD2 in the ileum (p < 0.05). The results of 16S rRNA sequencing showed that CGA altered the ileal microbiota composition and increased the relative abundance of Lactobacillus reuteri and Lactobacillus pontis (p < 0.05). Consistently, the findings suggested that the enhancement of the intestinal barrier in piglets was associated with increased concentrations of T-AOC, IL-22, and sIgA in the serum and T-AOC, T-SOD, and sIgA in the jejunum, as well as T-AOC and CAT in the ileum caused by CGA (p < 0.05). Meanwhile, CGA decreased the concentrations of MDA, IL-1β, IL-6, and TNF-α in the serum and jejunum and IL-1β and IL-6 in the ileum (p < 0.05). Importantly, this study found that CGA alleviated intestinal inflammation and oxidative stress in the piglets by inhibiting the TLR4/NF-κB signaling pathway and activating the Nrf2 signaling pathway. These findings showed that CGA enhances the intestinal health of weaned piglets by inhibiting the TLR4/NF-κB pathway and activating the Nrf2 pathway.
The Link between Salivary Amylase Activity, Overweight, and Glucose Homeostasis
Authors: Erta Gita , Gersone Gita , Jurka Antra , Tretjakovs Pēteris
Published: September 2024

Butyrate, a short-chain fatty acid (SCFA) produced by the fermentation of dietary fibers in the colon, plays a pivotal role in regulating metabolic health, particularly by enhancing insulin sensitivity. Given the rising incidence of metabolic disorders, understanding the factors that influence butyrate production is of significant interest. This study explores the link between salivary amylase activity and butyrate levels in overweight women of reproductive age. Participants were categorized into low (LSA) and high (HSA) salivary amylase activity groups and further divided into two subgroups: one followed a low-starch diet (LS), and the other underwent caloric restriction (CR). We assessed salivary amylase activity and measured serum butyrate concentrations to examine their associations. Our findings showed a significant, though weak, positive correlation (ρ = 0.0486, p < 0.05), suggesting a link between salivary amylase activity and butyrate levels. The statistical significance, despite the weak correlation, implies that this relationship is not random. Moreover, higher baseline butyrate levels were observed in women with elevated salivary amylase activity. Also, women with low salivary amylase activity on a low-starch diet experienced a more pronounced increase in butyrate levels compared to those on caloric restriction. These results suggest that salivary amylase activity and dietary intake interact to influence butyrate production, with potential implications for improving insulin sensitivity and metabolic health. The study underscores the potential of butyrate in enhancing insulin sensitivity and promoting overall metabolic well-being. Further research is necessary to clarify the mechanisms involved and to understand the long-term effects of butyrate on metabolic health across different populations.
Biological Properties of the Mucus and Eggs of Helix aspersa Müller as a Potential Cosmetic and Pharmaceutical Raw Material: A Preliminary Study
Authors: Herman Anna , Wińska Patrycja , Białek Małgorzata , Herman Andrzej P.
Published: September 2024

In recent years, snail mucus (SM) has become popular as an active ingredient in cosmetic and pharmaceutical products. In turn, snail eggs (SEs) also seem to be a promising active compound, but the biological activities of SEs are significantly less known. Therefore, our preliminary study aimed to compare the biological activities of the SEs and SM of Helix aspersa Müller. The metabolomic analysis (LC–MS technique), determination of the antimicrobial activity (agar diffusion test, broth microdilution methods), antioxidant activity (ABTS assay), cytotoxicity assay (MTT), and proapoptotic properties (flow cytometry) of the SEs and SM were evaluated. It was found that the SEs and SM contain 8005 and 7837 compounds, respectively. The SEs showed antibacterial activity against S. aureus (MIC 12.5 mg/mL) and P. aeruginosa (MIC 3.12 mg/mL). The EC50 estimation of the antioxidant activity is 89.64 mg/mL and above 100 mg/mL for the SEs and SM, respectively. The SEs also inhibited the cell proliferation of cancer cell lines (HCT-116, MCF-7, HT-29) more strongly compared to the SM. The highest proportion of apoptotic cells in HCT-116 was observed. The reach composition of the compounds in the SEs and SM may be crucial for the creation of new cosmetic and pharmaceutical raw materials with different biological activities. However, further extended studies on the biological activities of H. aspersa-delivered materials are still necessary.
Mechanistic Insight into the Enantioselective Degradation of Esterase QeH to (R)/(S)–Quizalofop–Ethyl with Molecular Dynamics Simulation Using a Residue-Specific Force Field
Authors: Zhu Yu-Meng , Yao Gui , Shao Song , Liu Xin-Yu , Xu Jun , Chen Chun , Zhang Xing-Wang , Huang Zhuo-Ran , Xu Cheng-Zhen , Zhang Long , Wu Xiao-Min
Published: September 2024

The enantioselective mechanism of the esterase QeH against the two enantiomers of quizalofop–ethyl (QE) has been primitively studied using computational and experimental approaches. However, it is still unclear how the esterase QeH adjusts its conformation to adapt to substrate binding and promote enzyme–substrate interactions in the catalytic kinetics. The equilibrium processes of enzyme–substrate interactions and catalytic dynamics were reproduced by performing independent molecular dynamics (MD) runs on the QeH-(R)/(S)-QE complexes with a newly developed residue-specific force field (RSFF2C). Our results indicated that the benzene ring of the (R)-QE structure can simultaneously form anion–π and cation–π interactions with the side-chain group of Glu328 and Arg384 in the binding cavity of the QeH-(R)-QE complex, resulting in (R)-QE being closer to its catalytic triplet system (Ser78-Lys81-Tyr189) with the distances measured for the hydroxyl oxygen atom of the catalytic Ser78 of QeH and the carbonyl carbon atom of (R)-QE of 7.39 Å, compared to the 8.87 Å for (S)-QE, whereas the (S)-QE structure can only form an anion–π interaction with the side chain of Glu328 in the QeH-(S)-QE complex, being less close to its catalytic site. The computational alanine scanning mutation (CAS) calculations further demonstrated that the π–π stacking interaction between the indole ring of Trp351 and the benzene ring of (R)/(S)-QE contributed a lot to the binding stability of the enzyme–substrate (QeH-(R)/(S)-QE). These results facilitate the understanding of their catalytic processes and provide new theoretical guidance for the directional design of other key enzymes for the initial degradation of aryloxyphenoxypropionate (AOPP) herbicides with higher catalytic efficiencies.
Polyethylene Glycol/Pullulan-Based Carrier for Silymarin Delivery and Its Potential in Biomedical Applications
Authors: Iwaniec Julia , Niziołek Karina , Polanowski Patryk , Słota Dagmara , Kosińska Edyta , Sadlik Julia , Miernik Krzysztof , Jampilek Josef , Sobczak-Kupiec Agnieszka
Published: September 2024

Restoring the structures and functions of tissues along with organs in human bodies is a topic gathering attention nowadays. These issues are widely discussed in the context of regenerative medicine. Excipients/delivery systems play a key role in this topic, guaranteeing a positive impact on the effectiveness of the drugs or therapeutic substances supplied. Advances in materials engineering, particularly in the development of hydrogel biomaterials, have influenced the idea of creating an innovative material that could serve as a carrier for active substances while ensuring biocompatibility and meeting all the stringent requirements imposed on medical materials. This work presents the preparation of a natural polymeric material based on pullulan modified with silymarin, which belongs to the group of flavonoids and derives from a plant called Silybum marianum. Under UV light, matrices with a previously prepared composition were crosslinked. Before proceeding to the next stage of the research, the purity of the composition of the matrices was checked using Fourier-transform infrared (FT-IR) spectroscopy. Incubation tests lasting 19 days were carried out using incubation fluids such as simulated body fluid (SBF), Ringer’s solution, and artificial saliva. Changes in pH, electrolytic conductivity, and weight were observed and then used to determine the sorption capacity. During incubation, SBF proved to be the most stable fluid, with a pH level of 7.6–7.8. Sorption tests showed a high sorption capacity of samples incubated in both Ringer’s solution and artificial saliva (approximately 350%) and SBF (approximately 300%). After incubation, the surface morphology was analyzed using an optical microscope for samples demonstrating the greatest changes over time. The active substance, silymarin, was released using a water bath, and then the antioxidant capacity was determined using the Folin–Ciocâlteu test. The tests carried out proved that the material produced is active and harmless, which was shown by the incubation analysis. The continuous release of the active ingredient increases the biological value of the biomaterial. The material requires further research, including a more detailed assessment of its balance; however, it demonstrates promising potential for further experiments.
New Insights into Mitochondria in Health and Diseases
Authors: Li Ya , Zhang Huhu , Yu Chunjuan , Dong Xiaolei , Yang Fanghao , Wang Mengjun , Wen Ziyuan , Su Mohan , Li Bing , Yang Lina
Published: September 2024

Mitochondria are a unique type of semi-autonomous organelle within the cell that carry out essential functions crucial for the cell’s survival and well-being. They are the location where eukaryotic cells carry out energy metabolism. Aside from producing the majority of ATP through oxidative phosphorylation, which provides essential energy for cellular functions, mitochondria also participate in other metabolic processes within the cell, such as the electron transport chain, citric acid cycle, and β-oxidation of fatty acids. Furthermore, mitochondria regulate the production and elimination of ROS, the synthesis of nucleotides and amino acids, the balance of calcium ions, and the process of cell death. Therefore, it is widely accepted that mitochondrial dysfunction is a factor that causes or contributes to the development and advancement of various diseases. These include common systemic diseases, such as aging, diabetes, Parkinson’s disease, and cancer, as well as rare metabolic disorders, like Kearns–Sayre syndrome, Leigh disease, and mitochondrial myopathy. This overview outlines the various mechanisms by which mitochondria are involved in numerous illnesses and cellular physiological activities. Additionally, it provides new discoveries regarding the involvement of mitochondria in both disorders and the maintenance of good health.
The BRD4 Inhibitor I-BET-762 Reduces HO-1 Expression in Macrophages and the Pancreas of Mice
Authors: Leal Ana S. , Liby Karen T.
Published: September 2024

In pancreatic cancer, the tumor microenvironment (TME) accounts for up to 90% of the tumor mass. Pancreatitis, characterized by the increased infiltration of macrophages into the pancreas, is a known risk factor for pancreatic cancer. The NRF2 (nuclear factor erythroid 2-related factor 2) transcription factor regulates responses to oxidative stress and can promote cancer and chemoresistance. NRF2 also attenuates inflammation through the regulation of macrophage-specific genes. Heme oxygenase 1 (HO-1) is expressed by anti-inflammatory macrophages to degrade heme, and its expression is dependent on NRF2 translocation to the nucleus. In macrophages stimulated with conditioned media from pancreatic cancer cells, HO-1 protein levels increased, which correlated with higher NRF2 expression in the nuclear fraction. Significant differences in macrophage infiltration and HO-1 expression were detected in LSL-KrasG12D/+; Pdx-1-Cre (KC) mice, Nrf2 whole-body knockout (KO) mice and wildtype mice with pancreatitis. Since epigenetic modulation is a mechanism used by tumors to regulate the TME, using small molecules as epigenetic modulators to activate immune recognition is therapeutically desirable. When the bromodomain inhibitor I-BET-762 was used to treat macrophages or mice with pancreatitis, high levels of HO-1 were reduced. This study shows that bromodomain inhibitors can be used to prevent physiological responses to inflammation that promote tumorigenesis.
Companion Tests and Personalized Cancer Therapy: Reaching a Glass Ceiling
Authors: Ferrari Victoria , Mograbi Baharia , Gal Jocelyn , Milano Gérard
Published: September 2024

The use of companion diagnostics has become a standard in precision oncology in the context of ongoing therapeutic innovation. However, certain limitations make their application imperfect in current practice. This position paper underscores the need to broaden the notion of companion testing, considering the potential of emerging technologies, including computational biology, to overcome these limitations. This wave of progress should impact not only our representation of the analytical tool itself but also the nature of the tumoral sample under analysis (liquid biopsies). The complex inter-relationship between companion test guided-personalized therapy, and health agency policies for new drug agreements will also be discussed.
Tear Proteomics in Children and Adolescents with Type 1 Diabetes: A Promising Approach to Biomarker Identification of Diabetes Pathogenesis and Complications
Authors: Angelopoulou Eleni , Kitani Rosa-Anna , Stroggilos Rafael , Lygirou Vasiliki , Vasilakis Ioannis-Anargyros , Letsou Konstantina , Vlahou Antonia , Zoidakis Jerome , Samiotaki Martina , Kanaka-Gantenbein Christina , Nicolaides Nicolas C.
Published: September 2024

The aim of the current study was to investigate the tear proteome in children and adolescents with type 1 diabetes (T1D) compared to healthy controls, and to identify differences in the tear proteome of children with T1D depending on different characteristics of the disease. Fifty-six children with T1D at least one year after diagnosis, aged 6–17 years old, and fifty-six healthy age- and sex-matched controls were enrolled in this cross-sectional study. The proteomic analysis was based on liquid chromatography tandem mass spectrometry (LC-MS/MS) enabling the identification and quantification of the protein content via Data-Independent Acquisition by Neural Networks (DIA-NN). Data are available via ProteomeXchange with the identifier PXD052994. In total, 3302 proteins were identified from tear samples. Two hundred thirty-nine tear proteins were differentially expressed in children with T1D compared to healthy controls. Most of them were involved in the immune response, tissue homeostasis and inflammation. The presence of diabetic ketoacidosis at diagnosis and the level of glycemic control of children with T1D influenced the tear proteome. Tear proteomics analysis revealed a different proteome pattern in children with T1D compared to healthy controls offering insights on deregulated biological processes underlying the pathogenesis of T1D. Differences within the T1D group could unravel biomarkers for early detection of long-term complications of T1D.
Functional Interdependence of Anoctamins May Influence Conclusions from Overexpression Studies
Authors: Ousingsawat Jiraporn , Schreiber Rainer , Kunzelmann Karl
Published: September 2024

Anoctamin 6 (ANO6, TMEM16F) is a phospholipid (PL) scramblase that moves PLs between both plasma membrane (PM) leaflets and operates as an ion channel. It plays a role in development and is essential for hemostasis, bone mineralization and immune defense. However, ANO6 has also been shown to regulate cellular Ca2+ signaling and PM compartments, thereby controlling the expression of ion channels such as CFTR. Given these pleiotropic effects, we investigated the functional interdependence of the ubiquitous ANO6 with other commonly co-expressed anoctamins. As most expression studies on anoctamins use HEK293 human embryonic kidney cells, we compared ion currents, PL scrambling and Ca2+ signals induced by the overexpression of anoctamins in HEK293 wild-type parental and ANO6-knockout cells. The data suggest that the endogenous expression of ANO6 significantly affects the results obtained from overexpressed anoctamins, particularly after increasing intracellular Ca2+. Thus, a significant interdependence of anoctamins may influence the interpretation of data obtained from the functional analysis of overexpressed anoctamins.
Student-Centered Active Learning Improves Performance in Solving Higher-Level Cognitive Questions in Health Sciences Education
Authors: Martín-Alguacil Nieves , Avedillo Luis
Published: September 2024

Student-centered active learning (SCAL) shifts the focus from the teacher to the student. Implementing SCAL requires the development of new forms of assessment beyond memorization and comprehension. This paper aims to demonstrate the effectiveness of SCAL by analyzing student performance at different cognitive levels. In flipped classrooms, students completed tasks with varying cognitive demands. The tests measured knowledge (level 1), comprehension (level 2), application (level 3) and analysis (level 4). This approach to assessment assesses not only the acquisition of content, but also skills that are critical to a health science student’s future career. The results of expository learning were compared with student-centered collaborative learning in the Anatomy and Embryology I course over three academic years. Student opinions were collected through 326 anonymous Wooclap® (Version: 2019101500) surveys. No differences in performance were found for low-cognitive-level questions. However, SCAL significantly improved performance on higher-cognitive-level questions that required problem solving and application of knowledge. Despite the benefits of SCAL, it requires more effort from both teachers and students. The current assessment system at Universidad Complutense, which measures teaching quality primarily in terms of student satisfaction, tends to penalize efforts to innovate. Many students are attracted to passive learning techniques because they provide a clear and structured path to success. This approach, which focuses on memorizing information for exams, provides a sense of security. Teachers need to have a strong belief in the effectiveness of SCAL methods to persist in their implementation.
Exploring Players’ Perspectives: A Comprehensive Topic Modeling Case Study on Elden Ring
Authors: Dehghani Fatemeh , Zaman Loutfouz
Published: September 2024

Game reviews heavily influence public perception. User feedback is crucial for developers, offering valuable insights to enhance game quality. In this research, Metacritic game reviews for Elden Ring were analyzed for topic modeling using Latent Dirichlet Allocation (LDA), Bidirectional Encoder Representations from Transformers (BERT), and a hybrid model combining both to identify effective methods for extracting underlying themes in player feedback. We analyzed and interpreted these models’ outputs to learn the game reviews. We aimed to identify the differences, similarities, and variations between the three to determine which provided more valuable and instructive information. Our findings indicate that each method successfully identified keywords with some similarities in identified words. The LDA model had the highest silhouette score, indicating the most distinct clustering. The LDA-BERT model had a 1% higher coherence score than LDA, indicating more meaningful topics.
Adaptive and Scalable Database Management with Machine Learning Integration: A PostgreSQL Case Study
Authors: Abbasi Maryam , Bernardo Marco V. , Váz Paulo , Silva José , Martins Pedro
Published: September 2024

The increasing complexity of managing modern database systems, particularly in terms of optimizing query performance for large datasets, presents significant challenges that traditional methods often fail to address. This paper proposes a comprehensive framework for integrating advanced machine learning (ML) models within the architecture of a database management system (DBMS), with a specific focus on PostgreSQL. Our approach leverages a combination of supervised and unsupervised learning techniques to predict query execution times, optimize performance, and dynamically manage workloads. Unlike existing solutions that address specific optimization tasks in isolation, our framework provides a unified platform that supports real-time model inference and automatic database configuration adjustments based on workload patterns. A key contribution of our work is the integration of ML capabilities directly into the DBMS engine, enabling seamless interaction between the ML models and the query optimization process. This integration allows for the automatic retraining of models and dynamic workload management, resulting in substantial improvements in both query response times and overall system throughput. Our evaluations using the Transaction Processing Performance Council Decision Support (TPC-DS) benchmark dataset at scale factors of 100 GB, 1 TB, and 10 TB demonstrate a reduction of up to 42% in query execution times and a 74% improvement in throughput compared with traditional approaches. Additionally, we address challenges such as potential conflicts in tuning recommendations and the performance overhead associated with ML integration, providing insights for future research directions. This study is motivated by the need for autonomous tuning mechanisms to manage large-scale, heterogeneous workloads while answering key research questions, such as the following: (1) How can machine learning models be integrated into a DBMS to improve query optimization and workload management? (2) What performance improvements can be achieved through dynamic configuration tuning based on real-time workload patterns? Our results suggest that the proposed framework significantly reduces the need for manual database administration while effectively adapting to evolving workloads, offering a robust solution for modern large-scale data environments.
The Biology, Impact, and Management of Xyleborus Beetles: A Comprehensive Review
Authors: Rodríguez-Becerra Sared Helena , Vázquez-Rivera Rafael , Ventura-Hernández Karla Irazú , Pawar Tushar Janardan , Olivares-Romero José Luis
Published: September 2024

Xyleborus beetles, a diverse group of ambrosia beetles, present challenges to forestry and agriculture due to their damaging burrowing behavior and symbiotic relationships with fungi. This review synthesizes current knowledge on the biology, ecology, and management of Xyleborus. We explore the beetles’ life cycle, reproductive strategies, habitat preferences, and feeding habits, emphasizing their ecological and economic impacts. Control and management strategies, including preventive measures, chemical and biological control, and integrated pest management (IPM), are critically evaluated. Recent advances in molecular genetics and behavioral studies offer insights into genetic diversity, population structure, and host selection mechanisms. Despite progress, managing Xyleborus effectively remains challenging. This review identifies future research needs and highlights innovative control methods, such as biopesticides and pheromone-based trapping systems.
Global Distribution Prediction of Cyrtotrachelus buqueti Guer (Coleoptera: Curculionidae) Insights from the Optimised MaxEnt Model
Authors: Peng Yaqin , Yang Junyi , Xu Danping , Zhuo Zhihang
Published: September 2024

Cyrtotrachelus buqueti Guer is a major pest affecting bamboo forests economically, causing significant damage to bamboo forests in Sichuan Province, China. To understand how C. buqueti responds to future climate conditions, an optimized Maximum Entropy Model (Maxent) was used to simulate the potential global distribution patterns of C. buqueti under current climate conditions and three different future climate scenarios and to analyze the dominant factors influencing its distribution. The results indicate that Bio18 (precipitation of the warmest quarter), Bio04 (temperature seasonality), Bio06 (minimum temperature of the coldest month), and Bio02 (mean diurnal temperature range) are the main environmental factors affecting the distribution of this species. The global area of high-suitability habitats for C. buqueti is 9.00 × 104 km2, primarily distributed in China. Under three different future climate scenarios, there are varying degrees of expansion in both the total suitable habitat and the medium-suitability areas for C. buqueti. Under the SSP5-8.5 scenario, the medium-suitability area of the species increases the most, reaching 9.83 × 104 km2. Additionally, these findings can serve as a reference for developing and implementing control strategies, assisting relevant authorities in more effectively managing and controlling this pest, and mitigating its potential threats to bamboo forest ecosystems and economies.
A Comparative Analysis of Different Xenorhabdus Strains Reveals a Virulent Factor, Cyclic Pro-Phe, Using a Differential Expression Profile Analysis of Non-Ribosomal Peptide Synthetases
Authors: Jin Gahyeon , Khan Falguni , Kim Yonggyun
Published: September 2024

Entomopathogenic bacteria, classified into the genus Xenorhabdus, exhibit a dual lifestyle as mutualistic symbionts to Steinernema nematodes and as pathogens to a broad range of insects. Bacterial virulence depends on toxin proteins that induce toxemia and various immunosuppressive secondary metabolites that cause septicemia. Particularly, the immunosuppressive properties of Xenorhabdus bacteria determine the variability of their insecticidal activities. This study explored the role of peptide metabolites in virulence and its variation among six bacterial strains across three species: X. nematophila, X. bovienii, and X. hominickii. Initially, their virulence significantly varied against a susceptible lepidopteran host, Maruca vitrata, but showed less variation against a tolerant coleopteran host, Tenebrio molitor, with high median lethal bacterial doses. In M. vitrata, virulence was strongly correlated with bacterial growth rate and inhibitory activity against phospholipase A2. Secondly, the six strains differed in the compositions of their secreted secondary metabolites, analyzed by GC-MS following ethyl acetate extraction. Notably, there was significant variation in the production of di- or tetra-peptides. Highly virulent strains commonly produced the cyclic Pro-Phe (cPF). Thirdly, the expression of non-ribosomal peptide synthetase (NRPS) genes varied greatly among the strains. NRPS genes were minimally expressed in the tolerant T. molitor and highly expressed in the susceptible M. vitrata. In M. vitrata, specific NRPS genes were markedly expressed in the virulent strains. Finally, cPF demonstrated potent immunosuppressive activity against the cellular and humoral responses of M. vitrata. The addition of cPF significantly enhanced the virulence against the tolerant T. molitor. These findings suggest that immunosuppression is necessary for the pathogenicity of Xenorhabdus bacteria, wherein NRPS products play a critical role in suppressing immune-associated factors in target insects.
Research Status of Sarcosaprophagous Beetles as Forensic Indicators
Authors: Shao Shipeng , Liu Siqi , Li Liangliang , Hu Gengwang , Zhang Yingna , Wang Yu
Published: September 2024

In forensic entomology, research focused on sarcosaprophagous flies, but the sarcosaprophagous beetles, as important “forensic indicator species” of late-stage PMI in cadaver decomposition, received less attention. To increase attention on, and use and understanding of, sarcosaprophagous beetles in forensic entomology, this paper presents a bibliometric analysis of the available relevant literature. The occurrence frequency of beetle families and species from succession studies, actual cases, and experiments were calculated and illustrated using graphs. As a result, a total of 14 families and 1077 species associated with carcasses were collected, with Staphylinidae being the most frequently recorded among the families, and Necrobia rufipes (Fabricius, 1781) (Coleoptera: Cleridae) being the most frequently recorded species. In addition, a brief introduction of the cadaver-related beetles of each family is given, and research on the species identification of the immature stages, age estimation of the immature stages, and estimation of the arrival time of sarcosaprophagous beetles are discussed and prospected. This work will aid in the increased use of sarcosaprophagous beetles in forensic science practice in the future.
Synergistic Larvicidal and Pupicidal Toxicity and the Morphological Impact of the Dengue Vector (Aedes aegypti) Induced by Geranial and trans-Cinnamaldehyde
Authors: Sittichok Sirawut , Passara Hataichanok , Sinthusiri Jirisuda , Moungthipmalai Tanapoom , Puwanard Cheepchanok , Murata Kouhei , Soonwera Mayura
Published: September 2024

Monoterpenes are effective and eco-friendly alternatives to conventional chemical larvicides. We tested single and binary mixtures of monoterpenes—geranial and trans-cinnamaldehyde—for their larvicidal and pupicidal activities against Aedes aegypti L. and for non-target toxicity on guppies (Poecilia reticulata Peters), using 1% (w/w) temephos as a reference. Geranial and trans-cinnamaldehyde at 250 ppm showed stronger larvicidal and pupicidal activities with a 100% mortality rate and an LT50 ranging from 0.3 to 0.6 h. All combinations were strongly synergistic against larvae and pupae compared to single formulations, with an increased mortality value (IMV) of 6% to 93%. The combination of geranial + trans-cinnamaldehyde (1:1) at 200 ppm showed the highest impact, with an IMV of 93%. The strongest larvicidal and pupicidal activities, a 100% mortality rate, and an LT50 of 0.2 h were achieved by geranial + trans-cinnamaldehyde (1:1) 500 ppm. They were thirty times more effective than a 1% temephos solution (LT50 ranging from 6.7 to 96 h) and caused obviously shriveled cuticles and a swollen respiratory system. All single and binary mixtures were not toxic to the guppies. Thus, the combination of geranial + trans-cinnamaldehyde has great potential as a safe insecticide for controlling mosquito larvae and pupae.