bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Filter Ventilation and Expanded Tobacco on the Tar, Nicotine and Carbon Monoxide Yields from Cigarettes Sold in Australia
Authors: Winnall Wendy R. , Haynes Ashleigh , Klerx Walther , Bakker-‘t Hart Ingrid M. E. , Versluis Caroline , Leijten Niels M. , Brennan Emily , Talhout Reinskje , Wakefield Melanie A.
Published: December 2024

Cigarette brand variant names and characteristics such as the taste and feel of the smoke can mislead consumers into believing some products are less harmful. We assessed the characteristics of three common cigarette variants sold in Australia, “gold”, “blue” and “red”, to determine which characteristics differed by color, and which affected tar, nicotine and carbon monoxide (TNCO) yields. TNCO yields, physical parameters, expanded tobacco and filter ventilation were measured in cigarette color variants from eight brands. Filter ventilation and expanded tobacco were common across brands and variants. Compared to blue and red variants, gold variants had slightly shorter tobacco rods and greater filter ventilation. Gold variants had lower TNCO when measured using the industry-favored International Organization for Standardization (ISO) protocol. ISO-measured TNCO yields were associated with filter ventilation and tobacco rod length, but not use of expanded tobacco. When measured using the Health Canada Intensive (HCI) protocol, which better emulates human smoking behavior, TNCO emissions were markedly higher, and the emission differences by extent of filter ventilation were minimized, indicating that ISO measurements are misleading. These findings confirm that cigarette color names, and the filter ventilation levels they signify, remain misleading more than a decade after plain packaging eliminated pack colors in Australia, as higher levels of filter ventilation are not associated with reduced TNCO emissions measured using the HCI protocol. Consumer education and communication campaigns could amplify the impacts of Australia’s newly passed tobacco legislation banning color and other variant names that imply reduced harm.
Niobium-Containing Phosphate Glasses Prepared by the Liquid-Phase Method
Authors: Takahashi Minori , Shiraki Shota , Lee Sungho , Obata Akiko
Published: December 2024

Phosphate invert glasses (PIGs) have been attracting attention as materials for bone repair. PIGs have a high flexibility in chemical composition because they are composed of orthophosphate and pyrophosphate and can easily incorporate various ions in their glass networks. In our previous work, incorporation of niobium (Nb) into melt-quench-derived PIGs was effective in terms of controlling their ion release, and Nb ions promoted the activity of osteoblast-like cells. In the present work, a liquid-phase method was used for synthesizing Nb-containing PIGs, as this method allows us to prepare a glass precursor solution at room temperature, which can be attributed to improved glass-shape design. Nb-containing PIGs were successfully prepared, and their ion release behavior was controlled by changing the Nb content in the PIGs. The functions of Nb varied according to its content. For example, in the case of PIGs containing a larger amount of Nb, Nb acted as both the network modifier and former while also inducing the formation of chain-like structures. These glasses possessed a gradual ion release in a tris-HCl buffer solution. Cotton-wool-like structured scaffolds were fabricated using the synthesized Nb-containing glass using a wet-spinning method. Because the scaffolds possess excellent flexibility and controllable ion release, they are good candidates for new biomaterials.
Dyspareunia and Biomarkers: A Case Study of Sexual Dysfunction in Moderate Endometriosis
Authors: Nati Ionel Daniel , Ciortea Razvan , Malutan Andrei , Oancea Mihaela , Iuhas Cristian , Bucuri Carmen , Roman Maria , Ormindean Cristina , Gombos Leon , Mihu Dan
Published: December 2024

Endometriosis, a chronic hormone-dependent condition affecting 10% of women globally, impacts pelvic organs and occasionally distant sites, causing pain, infertility, and sexual dysfunction. Biomarkers such as IL-8, IL-10, and BDNF influence inflammation, nerve sensitization, and pain. This study investigates their relationship with sexual quality of life, focusing on dyspareunia and related dysfunctions, as assessed using the Female Sexual Function Index (FSFI). Dyspareunia, a prominent symptom of endometriosis, is linked to lower FSFI scores in domains such as desire (mean 3.38), satisfaction (mean 3.28), and pain (mean 3.07). Elevated IL-8 tissue levels negatively correlated with desire (r = −0.649, p < 0.05) and satisfaction (r = −0.813, p < 0.01). Similarly, higher BDNF tissue levels were associated with increased pain (r = −0.435, p < 0.01) and reduced satisfaction (r = −0.252, p < 0.05). Patient factors such as higher endometriosis severity scores (mean 26.3, p < 0.05) and surgical history correlated with lower desire and satisfaction. Conversely, physical activity improved pain scores (p < 0.01) and enhanced desire and lubrication (p < 0.05), likely through reduced inflammation and better circulation. These findings highlight the complex interplay between biomarkers, individual factors, and sexual dysfunction in endometriosis, underscoring the need for personalized therapeutic approaches.
Epigenetic Modulation of Estrogen Receptor Signaling in Ovarian Cancer
Authors: Skrzypczak Maciej , Wolinska Ewa , Adaszek Łukasz , Ortmann Olaf , Treeck Oliver
Published: December 2024

Ovarian cancer remains one of the leading causes of cancer-related deaths in women. There are several processes that are described to have a causal relationship in ovarian cancer development, progression, and metastasis formation, that occur both at the genetic and epigenetic level. One of the mechanisms involved in its pathogenesis and progression is estrogen signaling. Estrogen receptors (ER) α, ERβ, and G-protein coupled estrogen receptor 1 (GPER1), in concert with various coregulators and pioneer transcription factors, mediate the effects of estrogens primarily by the transcriptional regulation of estrogen responsive genes, thereby exerting pleiotropic effects including the regulation of cellular proliferation and apoptosis. The expression and activity of estrogen receptors and their coregulators have been demonstrated to be regulated by epigenetic mechanisms like histone modifications and DNA methylation. Here, we intend to summarize and to provide an update on the current understanding of epigenetic mechanisms regulating estrogen signaling and their role in ovarian cancer. For this purpose, we reviewed publications on this topic listed in the PubMed database. Finally, we assess to which extent drugs acting on the epigenetic level might be suitable for the treatment of ovarian cancer.
DNA Methylation Is Crucial for 1-Methylcyclopropene Delaying Postharvest Ripening and Senescence of Tomato Fruit
Authors: Wang Zhiqiang , Xie Jinmei , Duan Wenhui , Zhang Zhengke , Meng Lanhuan , Zhu Lisha , Wang Qing , Song Hongmiao , Xu Xiangbin
Published: December 2024

DNA methylation is an epigenetic modification process that can alter the functionality of a genome. It has been reported to be a key regulator of fruit ripening. In this study, the DNA methylation changes of CpG islands of ethylene signaling genes regulated by 1-methylcyclopropene (1-MCP) during ripening and senescence of tomato fruit were detected. The results showed that the 1-MCP treatment decreased the accumulation of lycopene, maintained the content of vitamin C, and delayed the ripening and senescence of tomato fruit. The quantitative real-time PCR and bisulfite sequencing analysis showed that 1-MCP treatment changed the expression and the DNA methylation level of CpG islands related to the ethylene signaling pathway genes, among which the DNA methylation change of LeEIN3 was the most significant. Compared with the control, 1-MCP treatment increased the DNA methylation level of the CpG island of the LeEIN3 gene, reduced the expression of LeEIN3 in tomato fruit, and was involved in 1-MCP delaying the postharvest senescence of tomato fruit. The results indicated that DNA methylation changes of ethylene signaling genes were involved in ethylene synthesis and signal transduction and played an important role in the regulation of 1-methylcyclopropene, delaying postharvest ripening and senescence of tomato fruit.
Anti-Inflammatory 8-Shogaol Mediates Apoptosis by Inducing Oxidative Stress and Sensitizes Radioresistance in Gastric Cancer
Authors: Kim Tae Woo , Lee Hee Gu
Published: December 2024

Radiotherapy is a powerful tumor therapeutic strategy for gastric cancer patients. However, radioresistance is a major obstacle to kill cancer cells. Ginger (Zingiber officinale Roscoe) exerts a potential function in various cancers and is a noble combined therapy to overcome radioresistance in gastric cancer radiotherapy. In this study, we suggested that 8-shogaol, a monomethoxybenzene compound extracted from Zingiber officinale Roscoe, has an anti-cancer and anti-inflammatory activity. In lipopolysaccharide (LPS)-induced inflammatory murine models in vivo and in vitro, 8-shogaol suppressed LPS-mediated cytokine production, including COX-2, TNFα, IL-6, and IL-1β. In xenograft mouse models of AGS gastric cancer cell lines, 8-shogaol reduced tumor volume. In gastric cancer cell lines AGS and NCI-N87, 8-shogaol reduced cell viability and increased caspase-3 activity and cytotoxicity LDH. However, combined with Z-VAD-FMK, 8-shogaol blocked caspase-dependent apoptotic cell death. 8-Shogaol induced intracellular reactive oxygen species (ROS) production, intracellular calcium (Ca2+) release, and endoplasmic reticulum (ER) stress response via the PERK-CHOP signaling pathway. Thapsigargin (TG), an ER stressor, mediated synergistic apoptosis and cell death in 8-shogaol-treated AGS and NCI-N87 cell lines. Nevertheless, loss of PERK or CHOP function suppressed ER-stress-induced apoptosis and cell death in 8-shogaol-treated AGS and NCI-N87 cell lines. 8-Shogaol-induced NADPH oxidase 4 (NOX4) activation is related to ROS generation. However, NOX4 knockdown and ROS inhibitors DPI or NAC blocked ER-stress-induced apoptosis by suppressing the inhibition of cell viability and the enhance of caspase-3 activity, intracellular ROS activity, and cytotoxicity LDH in 8-shogaol-treated AGS and NCI-N87 cell lines. Radioresistant gastric cancer models (AGSR and NCI-N87R) were developed and combined with 8-shogaol and radiation (2 Gy) to overcome radioresistance via the upregulation of N-cadherin and vimentin and the downregulation of E-cadherin. Therefore, these results indicated that 8-shogaol is a novel combined therapeutic strategy in gastric cancer radiotherapy.
Silk-Corn Zein Alloy Materials: Influence of Silk Types (Mori, Thai, Muga, Tussah, and Eri) on the Structure, Properties, and Functionality of Insect–Plant Protein Blends
Authors: Poluri Nagireddy , Gough Christopher R. , Sanderlin Steven , Velardo Christopher , Barca Anthony , Pinto Joseph , Perrotta Joseph , Cohen Maxwell , Hu Xiao
Published: December 2024

Biocompatible materials fabricated from natural protein polymers are an attractive alternative to conventional petroleum-based plastics. They offer a green, sustainable fabrication method while also opening new applications in biomedical sciences. Available from several sources in the wild and on domestic farms, silk is a widely used biopolymer and one of the strongest natural materials. This study aims to compare five different types of silk (Mori, Thai, Muga, Tussah, and Eri) fabricated into thin composite films in conjunction with plant-based proteins. To offer a wider range of morphologies, corn zein, another widely available protein material, was introduced into the silk protein networks to form blended polymers with various ratios of silk to zein. This resulted in the successful alloying of protein from an animal source with protein from a plant source. The material properties were confirmed through structural, morphological, and thermal analyses. FTIR analysis revealed the dominance of intramolecular beta-sheet structures in wild silks, while the domestic silks and zein favored random coil and alpha-helical structures, respectively. Post-treatments using water annealing further refined the structure and morphology of the films, resulting in stable composites with both inter- and intramolecular beta-sheet structures in wild silks. While in domestic silks, the random coils were converted into intermolecular beta-sheets with enhanced beta-sheet crystallinity. This improvement significantly enhanced the thermal and structural properties of the materials. By deciding on the source, ratio, and treatment of these biopolymers, it is possible to tailor protein blends for a wide range of applications in medicine, tissue engineering, food packaging, drug delivery, and bio-optics.
Identification of Disease-Relevant, Sex-Based Proteomic Differences in iPSC-Derived Vascular Smooth Muscle Cells
Authors: Ariyasinghe Nethika R. , Gupta Divya , Escopete Sean , Rai Deepika , Stotland Aleksandr , Sundararaman Niveda , Ngu Benjamin , Dabke Kruttika , McCarthy Liam , Santos Roberta S. , McCain Megan L. , Sareen Dhruv , Parker Sarah J.
Published: December 2024

The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insights into some aspects of human biology; however, not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology. Our analysis confirmed that differentiated cells have a proteomic profile more similar to healthy primary aortic smooth muscle cells than iPSCs. We also identified sex-based differences in iPSC-derived vascular smooth muscle cells in pathways related to ATP binding, glycogen metabolic process, and cadherin binding as well as multiple proteins relevant to cardiovascular pathophysiology and disease. Additionally, we explored the role of autosomal and sex chromosomes in protein regulation, identifying that proteins on autosomal chromosomes also show sex-based regulation that may affect the protein expression of proteins from autosomal chromosomes. This work supports the biological relevance of iPSC-derived vascular smooth muscle cells as a model for disease, and further exploration of the pathways identified here can lead to the discovery of sex-specific pharmacological targets for cardiovascular disease.
GmARF15 Enhances the Resistance of Soybean to Phytophthora sojae by Promoting GmPT10d Expression in Response to Salicylic Acid Signalling
Authors: Huo Yuhan , Chen Haiyuan , Zhang Zhuo , Song Yang , Liu Siyan , Wang Piwu , Fan Sujie
Published: December 2024

Phytophthora root and stem rot caused by Phytophthora sojae (P. sojae) is a globally prevalent oomycete disease. The use of resistant cultivars is an effective and environmentally friendly strategy to manage this disease. It is important to understand the molecular mechanisms underlying the response of Glycine max (soybean) to P. sojae infection. In this study, we demonstrated that an isoflavonoid-specific prenyltransferase gene (GmPT10d, Glyma.10G070300) was significantly upregulated in the soybean cultivar Williams 82 with high resistance to P. sojae infection. Transgenic soybean seedlings overexpressing GmPT10d exhibited enhanced resistance to P. sojae, and those subjected to RNA interference showed increased susceptibility to the pathogen. Yeast-one-hybrid and electrophoretic mobility shift assays revealed that GmARF15 could directly bind to the promoter of GmPT10d. Further analysis of the GmARF15 function showed that transgenic soybean seedlings overexpressing GmARF15 also exhibited enhanced resistance to P. sojae. Transactivation assay, luciferase assay, and qPCR analysis showed that GmARF15 could promote the expression of GmPT10d. Further analysis indicated that elevated salicylic acid levels were associated with increased expression of GmARF15 and GmPT10d. Taken together, these findings reveal a regulatory mechanism by which GmARF15 enhances soybean resistance to P. sojae, potentially by promoting the expression of GmPT10d through the salicylic acid signaling pathway.
Irbesartan May Ameliorate Ventricular Remodeling by Inhibiting CREB-Mediated Cardiac Aldosterone Synthesis in Rats with Myocardial Infarction
Authors: Li Jie , Lu Guihua , Deng Haiwei , Gao Xiuren , Zhai Yuansheng
Published: December 2024

Irbesartan improves ventricular remodeling (VR) following myocardial infarction (MI). This study investigates whether irbesartan attenuates VR by reducing aldosterone production in the heart and its underlying mechanisms. MI was induced in male Sprague–Dawley rats through coronary artery ligation. The MI rats were randomly assigned to two groups: one received a vehicle, and the other received 100 mg/kg/day of irbesartan for 5 weeks. Cardiac function and myocardial fibrosis were assessed using echocardiography and Masson’s trichrome staining, respectively. The impact of angiotensin II (Ang II) stimulation on cardiac microvascular endothelial cells (CMECs) from commercial sources was determined using ELISA, real-time PCR, and Western blotting. Irbesartan reduced left ventricular mass index, collagen composition, and aldosterone levels while enhancing cardiac function in MI rats. In vitro, Ang II time-dependently stimulated aldosterone secretion and CYP11B2 mRNA expression in CMECs (p < 0.05). Additionally, Ang II significantly upregulated p-CREB protein levels. However, these effects were abrogated by irbesartan and partially attenuated by CaMK inhibitor KN93 (p < 0.05). In conclusion, our study demonstrated that improvement in VR by irbesartan coincided with reduced CREB phosphorylation in CMECs and reduced aldosterone synthesis in the non-infarcted tissue. These effects may be mediated by blocking the AT1 receptor.
Identifying Strong Neoantigen MHC-I/II Binding Candidates for Targeted Immunotherapy with SINE
Authors: Bendik Joseph , Castro Andrea , Califano Joseph , Carter Hannah , Guo Theresa
Published: December 2024

The discovery of tumor-derived neoantigens which elicit an immune response through major histocompatibility complex (MHC-I/II) binding has led to significant advancements in immunotherapy. While many neoantigens have been discovered through the identification of non-synonymous mutations, the rate of these is low in some cancers, including head and neck squamous cell carcinoma. Therefore, the identification of neoantigens through additional means, such as aberrant splicing, is necessary. To achieve this, we developed the splice isoform neoantigen evaluator (SINE) pipeline. Our tool documents peptides present on spliced or inserted genomic regions of interest using Patient Harmonic-mean Best Rank scores, calculating the MHC-I/II binding affinity across the complete human leukocyte antigen landscape. Here, we found 125 potentially immunogenic events and 9 principal binders in a cohort of head and neck cancer patients where the corresponding wild-type peptides display no MHC-I/II affinity. Further, in a melanoma cohort of patients treated with anti-PD1 therapy, the expression of immunogenic splicing events identified by SINE predicted response, potentially indicating the existence of immune editing in these tumors. Overall, we demonstrate SINE’s ability to identify clinically relevant immunogenic neojunctions, thus acting as a useful tool for researchers seeking to understand the neoantigen landscape from aberrant splicing in cancer.
You Win Some, You Lose Some: Modifying the Molecular Periphery of Nitrofuran-Tagged Diazaspirooctane Reshapes Its Antibacterial Activity Profile
Authors: Vinogradova Lyubov , Komarova Kristina , Lukin Alexey , Zhuravlev Maxim , Deniskin Dmitry , Poliakova Anastasia , Chudinov Mikhail , Gureev Maxim , Dogonadze Marine , Vinogradova Tatiana , Rogacheva Elizaveta , Kraeva Lyudmila , Porozov Yuri , Korzhikov-Vlakh Viktor
Published: December 2024

The use of the concept of privileged structures significantly accelerates the search for new leads and their optimization. 6-(methylsulfonyl)-8-(4-methyl-4H-1,2,4-triazol-3-yl)-2-(5-nitro-2-furoyl)-2,6-diazaspiro[3.4]octane 1 has been identified as a lead, with MICs of 0.0124–0.0441 μg/mL against MTb multiresistant strains. Several series of structural analogues have been synthesized, including variations in the periphery and simplifications of their scaffolds. All synthesized compounds were tested against the MTb H37Rv strain and ESKAPE panel of pathogens using serial broth dilutions. However, an attempt to optimize structure of 1 did not lead to the development of more active compounds which can work against MTb, but to substances with high activity against S. aureus. Induced-fit docking and MM-GBSA calculations determined a change in the likely biotarget from deazaflavin-dependent nitroreductase to azoreductases. The privileged nature of the scaffold was demonstrated by the detection of a different type of activity.
Special Issue “New Molecular Insights into Ischemia/Reperfusion”
Authors: Ahn Ji Hyeon , Won Moo-Ho
Published: December 2024

Ischemia/reperfusion (IR) injury is a complex pathophysiological process in which the restoration of blood flow to ischemic tissue paradoxically exacerbates tissue damage and death [...]
Exploring the Role of Carbon Monoxide in Seed Physiology: Implications for Stress Tolerance and Practical Uses
Authors: Bazvand Faezeh , Wojtyla Łukasz , Eisvand Hamid Reza , Garnczarska Małgorzata , Adamiec Małgorzata
Published: December 2024

Carbon monoxide (CO) is recognized as a signaling molecule in plants, inducing various physiological responses. This article briefly examines the physiological functions of CO in seed biology and seedlings’ responses to environmental stresses. The activity of heme oxygenase (HO), the main enzyme responsible for CO synthesis, is a key factor controlling CO levels in plant cells. CO can influence seed germination by regulating seed dormancy through interactions with genes and hormones. Additionally, CO positively affects seedling growth by enhancing the antioxidant system, thereby increasing resistance to oxidative damage caused by stress. CO has beneficial effects on root development, root length, stomatal closure, and regulation of the photosynthetic system. Its interaction with reactive oxygen species (ROS) mediates hormone- and light-dependent growth processes during the early stages of plant development under stress. Furthermore, CO interacts with other signaling molecules, such as nitric oxide (NO), molecular hydrogen (H2), and hydrogen sulfide (H2S). By gaining a better understanding of the molecular mechanisms underlying these processes, CO can be more effectively utilized to improve seed germination and seedling growth in agricultural practices.
Development of Drug-Induced Gene Expression Ranking Analysis (DIGERA) and Its Application to Virtual Screening for Poly (ADP-Ribose) Polymerase 1 Inhibitor
Authors: Cho Hyein , No Kyoung Tai , Lim Hocheol
Published: December 2024

Understanding drug-target interactions is crucial for identifying novel lead compounds, enhancing efficacy, and reducing toxicity. Phenotype-based approaches, like analyzing drug-induced gene expression changes, have shown effectiveness in drug discovery and precision medicine. However, experimentally determining gene expression for all relevant chemicals is impractical, limiting large-scale gene expression-based screening. In this study, we developed DIGERA (Drug-Induced Gene Expression Ranking Analysis), a Lasso-based ensemble framework utilizing LINCS L1000 data to predict drug-induced gene expression rankings. We created novel numerical features for chemicals, cell lines, and experimental conditions, allowing the prediction of gene expression rankings across eight key cell lines. DIGERA outperformed baseline models in the F1@K metric, demonstrating improved precision in gene expression ranking. We also combined DIGERA with an iterative fine-tuning process for de novo design, suggesting 10 PARP1 inhibitors with favorable predicted properties like binding affinity, synthetic accessibility, solubility, membrane permeability, drug-likeness, and similar gene expression ranking to olaparib. Notably, nine compounds were novel, and six analogs of these compounds had references linked to PARP1 inhibition. These results underscore DIGERA’s potential to boost model performance and robustness through novel features and ensemble learning, aiding virtual screening for new PARP1 inhibitors.
From High Protection to Lethal Effect: Diverse Outcomes of Immunization Against Invasive Candidiasis with Different Candida albicans Extracellular Vesicles
Authors: Martínez-López Raquel , Molero Gloria , Parra-Giraldo Claudia Marcela , Cabeza Matías Sebastián , Castejón Guillermo , García-Durán Carmen , Clemente Luis Felipe , Hernáez María Luisa , Gil Concha , Monteoliva Lucía
Published: December 2024

Extracellular vesicles (EVs) from Candida albicans can elicit immune responses, positioning them as promising acellular vaccine candidates. We characterized EVs from an avirulent C. albicans cell wall mutant (ecm33Δ) and evaluated their protective potential against invasive candidiasis. EVs from the yeast (YEVs) and hyphal (HEVs) forms of the SC5314 wild-type strain were also tested, yielding high survival rates with SC5314 YEV (91%) and ecm33 YEV immunization (64%). Surprisingly, HEV immunization showed a dual effect, resulting in 36% protection but also causing premature death in some mice. Proteomic analyses revealed distinct profiles among the top 100 proteins in the different EVs, which may explain these effects: a shared core of 50 immunogenic proteins such as Pgk1, Cdc19, and Fba1; unique, relevant immunogenic proteins in SC5314 YEVs; and proteins linked to pathogenesis, like Ece1 in SC5314 HEVs. Sera from SC5314 YEV-immunized mice showed the highest IgG2a titers and moderate IL-17, IFN-γ, and TNF-α levels, indicating the importance of both humoral and cellular responses for protection. These findings highlight the distinct immunogenic properties of C. albicans EVs, suggesting their potential in acellular vaccine development while emphasizing the need to carefully evaluate pathogenic risks associated with certain EVs.
The Role of Linoleic Acid in Skin and Hair Health: A Review
Authors: Wang Xi , Jia Yan , He Huaming
Published: December 2024

Lipids are intimately associated with skin condition. This review aims to discuss the function of linoleic acid (LA, 18:2, ω-6), an essential fatty acid, in skin health and hair growth. In skin, LA can be metabolized into ω-6 unsaturated fatty acid, oxidized derivatives and incorporated into complex lipid molecules, including ω-hydroxy-ceramides. Previous research has revealed that skin diseases including acne, atopic dermatitis and psoriasis are associated with disordered LA metabolism. Studies based on animal or skin cell models suggest that LA or LA-rich vegetable oils, topically applied, exhibit diverse biological activities, including the repair of the skin barrier, the promotion of wound healing, skin whitening, photoprotection, anti-inflammatory effects and the stimulation of hair growth. Moreover, the underlying mechanisms of LA’s beneficial effects on skin are summarized. Further research on the correlation of LA metabolism and skin disorders, a deeper exploration of the mechanisms underlying the function of LA in skin management and more investigations of its clinical application are required to enhance the understanding and utilization of LA in cosmetics and pharmaceuticals.
Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature
Authors: Moldasheva Aiman , Zhakupova Assem , Aljofan Mohamad
Published: December 2024

Metformin is an antidiabetic drug with reported potential antiproliferative activity against different cancer types including breast cancer. However, the mechanism of action of how metformin can induce its antiproliferative activity is still unclear. Thus, the current study is a systematic review of the literature aiming to explore the reported antiproliferative mechanisms of metformin against breast cancer. The study included seventeen research articles that describe different mechanisms of action against breast cancer. While the majority of the studies confirm the antiproliferative potential of metformin, albeit at different potencies, there appear to be various mechanisms and factors that can influence this effect. There are a number of questions yet to be answered pertaining the use of metformin as an anti-cancer agent, warranting further investigation into this emerging area of research.
Protein-Based Mechanism of Wheat Growth Under Salt Stress in Seeds Irradiated with Millimeter Waves
Authors: Komatsu Setsuko , Koh Rachel , Yamaguchi Hisateru , Hitachi Keisuke , Tsuchida Kunihiro
Published: December 2024

Wheat is one of the most extensively grown crops in the world; however, its productivity is reduced due to salinity. This study focused on millimeter wave (MMW) irradiation to clarify the salt-stress tolerance mechanism in wheat. In the present study, wheat-root growth, which was suppressed to 77.6% of the control level under salt stress, was recovered to the control level by MMW irradiation. To reveal the salt-stress tolerance mechanism of MMW irradiation on wheat, a proteomic analysis was conducted. Proteins related to cell cycle, proliferation, and transport in biological processes, as well as proteins related to the nucleus, cytoskeleton, and cytoplasm within cellular components, were inversely correlated with the number of proteins. The results of the proteomic analysis were verified by immunoblot and other analyses. Among the proteins related to the scavenging reactive-oxygen species, superoxide dismutase and glutathione reductase accumulated under salt stress and further increased in the MMW-irradiated wheat. Among pathogen-related proteins, pathogenesis-related protein 1 and the Bowman–Birk proteinase inhibitor decreased under salt stress and recovered to the control level in the MMW-irradiated wheat. The present results indicate that MMW irradiation of wheat seeds improves plant-growth recovery from salt stress through regulating the reactive oxygen species-scavenging system and the pathogen-related proteins. These genes may contribute to the development of salt-stress-tolerant wheat through marker-assisted breeding and genome editing.
Investigating the Impact of Circulating MicroRNAs on Knee and Hip Osteoarthritis: Causal Links, Biological Mechanisms, and Drug Interactions
Authors: Li Shanni , Peng Yihui , Yu Yang , Xu Hongjun , Yin Zhaojing , Du Yiyang , Ma Mingyang , Ji Zhongyin , Qian Wenwei
Published: December 2024

Osteoarthritis (OA), particularly in the knee and hip, poses a significant global health challenge due to limited therapeutic options. To elucidate the molecular mechanisms of OA and identify potential biomarkers and therapeutic targets, we utilized genome-wide association studies (GWAS) and cis-miRNA expression quantitative trait loci (cis-miR-eQTL) datasets to identify miRNAs associated with OA, revealing 16 that were linked to knee OA and 21 to hip OA. Among these, hsa-miR-1303 was significantly upregulated in both knee and hip OA (IVW: p = 6.8164×10−36 and 4.7919×10−2 respectively, OR > 1) and identified as a key factor in disease progression. Hsa-miR-1303 potentially regulates 30 genes involved in critical signaling pathways, such as the neurotrophin signaling pathway, and interacts with competing endogenous RNAs (ceRNAs) like circ_0041843 and LINC01338, thereby influencing key regulatory proteins such as SUMO2 and PARP1. Pharmacologically, hsa-miR-1303 targets nine druggable genes, including NRAS, H2AZ1, and RPS3, which have implications for drugs like cantharidin and diindolylmethane, potentially critical for developing novel OA treatments. Conversely, hsa-miR-125a-5p and hsa-miR-125b-5p, which are downregulated in both knee and hip OA, are associated with pathways such as HIF-1 and JAK-STAT, which modulate apoptotic signaling and transcriptional regulation. These miRNAs also interact with ceRNAs such as circ_0000254 and SPACA6P-AS, impacting proteins like STAT3, MCL1, and TRAF6. A drug interaction analysis identified 47 potential treatments, including Resveratrol and Acetaminophen, suggesting new therapeutic possibilities for OA management. This study not only highlights the role of miRNAs like hsa-miR-1303 and hsa-miR-125 in OA but also opens avenues for miRNA-based therapeutic development.
Molecular Signatures of Aeroallergen Sensitization in Respiratory Allergy: A Comparative Study Across Climate-Matched Populations
Authors: González-Pérez Ruperto , Galván-Calle César Alberto , Galán Tania , Poza-Guedes Paloma , Sánchez-Machín Inmaculada , Enrique-Calderón Oscar Manuel , Pineda Fernando
Published: December 2024

Climate change is significantly altering the dynamics of airborne allergens, affecting their seasonality, allergenicity, and geographic distribution, which correlates with increasing rates of allergic diseases. This study investigates aeroallergen sensitization among populations from Tenerife, Spain, and Lima, Peru—two regions with similar climates but distinct socio-economic conditions. Our findings reveal that Spanish individuals, particularly those with asthma, demonstrate higher sensitization levels to a broader range of allergens, especially mites, with 85% of participants reacting to at least one mite allergen. In contrast, Peruvian patients exhibit a narrower spectrum of sensitization. These results highlight the influence of environmental factors, such as pollution and socio-economic disparities, on allergen exposure and immune responses. Moreover, this study underscores the necessity for region-specific diagnostic and therapeutic strategies to effectively address these variations. By elucidating the intricate relationship between climate change, environmental factors, and allergen sensitization, this research offers insights into respiratory allergic conditions, advocating for tailored interventions to mitigate their impact across diverse populations.
Preconditioning with Wound Fluid Enhances Immunosuppressive Properties of Mesenchymal Stromal Cells In Vitro
Authors: Moratin Helena , Mache Isabel , Goncalves Miguel , Ehret Kasemo Totta , Stöth Manuel , Meyer Till Jasper , Hackenberg Stephan , Scherzad Agmal , Herrmann Marietta
Published: December 2024

Immunosuppression is one key feature of mesenchymal stromal cells (MSCs) that has high expectations for therapeutic use. The influence of pro-inflammatory stimuli can modify the characteristics of MSCs and enhance immunosuppressive properties. The local postoperative environment contains cytokines, MSCs, and immune cells in high quantities, and their mutual influence is still unclear. Knowledge of in vivo processes is pivotal for potential therapeutic applications, and therefore, the aim of this study was to investigate the influence of wound fluid (WF) on the immunomodulatory potential of MSCs. CD4+ cells were co-cultured with native or WF-preconditioned MSCs for 5 days. CFSE staining revealed significant suppression of T cell proliferation after co-culture that was even more distinct in co-culture with WF-MSCs. The concentration of IDO-1, TGF-β1 and IFN-γ was higher while TNF-α was reduced in co-culture supernatants, indicating a transition to an anti-inflammatory milieu. In summary, the results provide evidence that the influence of WF alters the immunomodulatory potential of MSCs. These findings should serve as the basis for further investigations with a focus on T cell subpopulations.
Group V Chitin Deacetylases Are Responsible for the Structure and Barrier Function of the Gut Peritrophic Matrix in the Chinese Oak Silkworm Antheraea pernyi
Authors: Tang Jing-Wen , Wang Qi , Jiang Yun-Min , Jiang Yi-Ren , Wang Yong , Liu Wei
Published: December 2024

Chitin deacetylases (CDAs) are carbohydrate esterases associated with chitin metabolism and the conversion of chitin into chitosan. Studies have demonstrated that chitin deacetylation is essential for chitin organization and compactness and therefore influences the mechanical and permeability properties of chitinous structures, such as the peritrophic membrane (PM) and cuticle. In the present study, two genes (ApCDA5a and ApCDA5b) encoding CDA protein isoforms were identified and characterized in Chinese oak silkworm (Antheraea pernyi) larvae. Although five signature motifs were identified, CDA5 proteins only have the chitin-deacetylated catalytic domain. Spatiotemporal expression pattern analyses revealed that both transcripts presented the highest abundance in the anterior region of the midgut during the feeding period after molting, suggesting their role in chitin turnover and PM assembly. The down-regulation of ApCDA5a and ApCDA5b via RNA interference (RNAi) was correlated with the breakage of chitin microfibrils in the PM, suggesting that group V CDAs were essential for the growth and assembly of the chitinous layer. Additionally, ApCDA5a and ApCDA5b may have non-overlapping functions that regulate the morphological characteristics of PM chitin construction in different ways. Larvae injected with double-stranded RNA (dsRNA) against ApCDA5a and ApCDA5b transcripts were less resistant to infection by N. pernyi than those in the control groups. These results revealed that down-regulating ApCDA5a and ApCDA5b had independent effects on the PM structure and undermined the intactness of the PM, which disrupted the function of the PM against microsporidia infection per os. Our data provide new evidence for differentiating CDA functions among group V CDAs in lepidopteran insects.
Nanoscale Characterization of Interaction of Nucleosomes with H1 Linker Histone
Authors: Rafa Ahmed Yesvi , Filliaux Shaun , Lyubchenko Yuri L.
Published: December 2024

In eukaryotic nuclei, DNA is wrapped around an octamer of core histones to form nucleosomes. H1 binds to the linker DNA of nucleosome to form the chromatosome, the next structural unit of chromatin. Structural features on individual chromatosomes contribute to chromatin structure, but not fully characterized. In addition to canonical nucleosomes composed of two copies each of histones H2A, H2B, H3, and H4 (H3 nucleosomes), centromeres chromatin contain nucleosomes in which H3 is replaced with its analog CENP-A, changing structural properties of CENP-A nucleosomes. Nothing is known about the interaction of H1 with CENP-A nucleosomes. Here we filled this gap and characterized the interaction of H1 histone with both types of nucleosomes. H1 does bind both types of the nucleosomes forming more compact chromosome particles with elevated affinity to H3 nucleosomes. H1 binding significantly increases the stability of chromatosomes preventing their spontaneous dissociation. In addition to binding to the entry-exit position of the DNA arms identified earlier, H1 is capable of bridging of distant DNA segments. H1 binding leads to the assembly of mononucleosomes in aggregates, stabilized by internucleosome interactions as well as bridging of the DNA arms of chromatosomes. Contribution of these finding to the chromatin structure and functions are discussed.
A Trusted Federated Learning Method Based on Consortium Blockchain
Authors: Yin Xiaojun , Wu Xijun , Zhang Xinming
Published: December 2024

Federated learning (FL) has gained significant attention in distributed machine learning due to its ability to protect data privacy while enabling model training across decentralized data sources. However, traditional FL methods face challenges in ensuring trust, security, and efficiency, particularly in heterogeneous environments with varying computational capacities. To address these issues, we propose a blockchain-based trusted federated learning method that integrates FL with consortium blockchain technology. This method leverages computational power registration to group participants with similar resources into private chains and employs cross-chain communication with a central management chain to ensure efficient and secure model aggregation. Our approach enhances communication efficiency by optimizing the model update process across chains, and it improves security through blockchain’s inherent transparency and immutability. The use of smart contracts for participant verification, model updates, and auditing further strengthens the trustworthiness of the system. Experimental results show significant improvements in communication efficiency, model convergence speed, and security compared to traditional federated learning methods. This blockchain-based solution provides a robust framework for creating secure, efficient, and scalable federated learning environments, ensuring reliable data sharing and trustworthy model training.
Research on the Construction of an Evaluation Index System for Onboard Equipment Status Based on Real-Time Data Analysis
Authors: Zou Fumin , Ye Ting , Guo Feng
Published: December 2024

The research explores methods for onboard real-time data analysis and health status assessment, focusing on the working principles and status assessment theory of onboard equipment in the electronic toll collection (ETC) system. By applying AHP, fuzzy comprehensive evaluation method, entropy method, and Delphi method, a practical health status assessment model for onboard equipment has been established, providing an innovative path for dynamic real-time monitoring of onboard devices. The research first constructs an indicator system and assessment model, combining expert scoring with fuzzy judgment to objectively quantify the status of onboard equipment, ultimately resulting in a health status assessment indicator system for the objects under evaluation. During the assessment process, expert scoring is used to determine the subjective weights via AHP, and the combined weights are derived by incorporating objective weights, with instance results showing that the comprehensive weights of various indicators lie between the subjective and objective weights. The research also utilizes the Weibull distribution to simulate the failure rate of onboard equipment, indicating that the failure modes of the onboard devices are closely related to their operational status, providing a theoretical basis for future technological improvements. Through empirical analysis of the assessment model, the research verifies the superiority of the comprehensive weights and emphasizes its new approach in health status assessment of onboard devices, opening up new avenues for research in related fields.
Life History Parameters of the Invasive Cotton Mealybug Phenacoccus solenopsis on Tomato at Four Constant Temperatures
Authors: Harbi Ahlem , Abbes Khaled , Chermiti Brahim , Suma Pompeo
Published: December 2024

The cotton mealybug, Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae), is an invasive polyphagous pest that has been reported in several tomato-producing Mediterranean countries. However, information regarding the impact of temperature variations on its potential damage and population dynamics on this crop is limited. The effect of four temperatures (20 ± 1 °C, 25 ± 1 °C, 30 ± 1 °C and 35 ± 1 °C) on the development, reproduction, and population growth parameters of P. solenopsis on tomatoes under controlled laboratory conditions was investigated using age-stage two-sex life tables. The increase in temperature caused a significant decrease in the developmental periods of all instars except eggs. The shortest durations of the life cycle (29.58 ± 0.28 days for females and 13.91 ± 0.25 days for males), the adult preoviposition period (APOP), and the total preoviposition period (TPOP) (APOP: 7.78 ± 0.09 days and TPOP: 18.33 ± 0.13 days) were obtained at 35 ± 1 °C. Fecundity varied with temperature, and the highest value was recorded at 30 ± 1 °C (183.29 ± 7.13 eggs/female). The highest average net reproduction rate (R0) (154.24 ± 14.681 offspring/female), intrinsic rate of increase (r) (0.222 ± 0.0036 d−1), and finite rate of increase (λ) (1.248 ± 0.00495 d−1) were observed at 35 ± 1 °C. A simulation of population increase and structure under different temperatures over a period of 90 days revealed that the greatest expected population size was at 35 ± 1 °C, with the completion of four overlapping generations. The data from this study provide valuable information for adapted pest management approaches against P. solenopsis on tomato crops.
Resistance of Wolbachia to Trimethoprim: Insights into Genes Encoding Dihydrofolate Reductase, Thymidylate Synthase and Serine Hydroxymethyltransferase in the Rickettsiales
Authors: Fallon Ann M.
Published: December 2024

Bacterial and eukaryotic dihydrofolate reductase (DHFR) enzymes are essential for DNA synthesis and are differentially sensitive to the competitive inhibitors trimethoprim and methotrexate. Unexpectedly, trimethoprim did not reduce Wolbachia abundance, and the wStri DHFR homolog contained amino acid substitutions associated with trimethoprim resistance in E. coli. A phylogenetic tree showed good association of DHFR protein sequences with supergroup A and B assignments. In contrast, DHFR is not encoded by wFol (supergroup E) and wBm (supergroup D) or by genomes of the closely related genera Anaplasma, Ehrlichia, Neorickettsia, and possibly Orientia. In E. coli and humans, DHFR participates in a coupled reactions with the conventional thymidylate synthase (TS) encoded by thyA to produce the dTMP required for DNA synthesis. In contrast, Wolbachia and other Rickettsiales express the unconventional FAD-TS enzyme encoded by thyX, even when folA is present. The exclusive use of FAD-TS suggests that Wolbachia DHFR provides a supplementary rather than an essential function for de novo synthesis of dTMP, possibly reflecting the relative availability of, and competing demands for, FAD and NAD coenzymes in the diverse intracellular environments of its hosts. Whether encoded by thyA or thyX, TS produces dTMP by transferring a methyl group from methylene tetrahydrofolate to dUMP. In the Rickettsiales, serine hydroxymethyltransferase (SMHT), encoded by a conserved glyA gene, regenerates methylene tetrahydrofolate. Unlike thyA, thyX lacks a human counterpart and thus provides a potential target for the treatment of infections caused by pathogenic members of the Rickettsiales.
The Interspecific Competition Between Larvae of Aedes aegypti and Major African Malaria Vectors in a Semi-Field System in Tanzania
Authors: Lushasi Sperancia Coelestine , Mwalugelo Yohana A. , Swai Johnson K. , Mmbando Arnold S. , Muyaga Letus L. , Nyolobi Nhandi K. , Mutashobya Anitha , Mmbaga Augustino T. , Kunambi Hamisi J. , Twaha Simoni , Mwema Mwema Felix , Lwetoijera Dickson W.
Published: December 2024

Interspecific competition between mosquito larvae may affects adult vectorial capacity, potentially reducing disease transmission. It also influences population dynamics, and cannibalistic and predatory behaviors. However, knowledge of interspecific competition between Ae. aegypti and Anopheles species is limited. The study examined interspecific competition between Ae. aegypti larvae and either An.arabiensis, An. gambiae, or An. funestus on individual fitness in semi-field settings. The experiments involved density combinations of 100:100, 200:0, and 0:200 (Ae. aegypti: Anopheles), reared with and without food, in small habitats (8.5 cm height × 15 cm diameter) with 0.5 liters of water and large habitats (15 cm height × 35 cm diameter) with 1 liter of water. The first group received Tetramin® fish food (0.02 g), while the second group was unfed to assess cannibalism and predation. While interspecific competition affected both genera, Anopheles species experienced greater effects, with reduced survival and delayed development, compared to Ae. aegypti. The mean wing lengths of all species were significantly small in small habitats with a mixed population (p < 0.001). The presence of food reduced cannibalism and predation compared to its absence. These interactions have implications for diseases transmission dynamics and can serve as biological indicators to signal the impacts of vector control interventions.