bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association of the Oral Microbiota with Cognitive Functioning in Adolescence
Authors: Naumova Oxana Y. , Dobrynin Pavel V. , Khafizova Galina V. , Grigorenko Elena L.
Published: September 2024

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host’s cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota. Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12–18 years and explored the associations between the microbiome and the youths’ cognitive performance captured with the Kaufman Assessment Battery for Children II (KABC-II). Results: Several bacterial species of the oral microbiota and related metabolic pathways were associated with cognitive function. In particular, we found negative associations between indicators of general intelligence and the relative abundance of Bacteroidetes and Lachnospiraceae and positive associations with Bifidobacteriaceae and Prevotella histicola sp. Among metabolic pathways, the super pathways related to bacterial cell division and GABA metabolism were linked to cognitive function. Conclusions: The results of our work are consistent with the literature reporting on the association between microbiota and cognitive function and support further population work to elucidate the potential for a healthy oral microbiome to improve cognitive health.
Genetic Mechanisms Involved in Microbial Stress Responses
Authors: Requena Jose M.
Published: September 2024

The ability of living beings to deal with abrupt environmental changes is paramount for survival, and organisms have evolved a large variety of molecular mechanisms (known globally as stress responses) to buffer the harmful effects of stressors on cellular homeostasis [...]
The VEGFA-Induced MAPK-AKT/PTEN/TGFβ Signal Pathway Enhances Progression and MDR in Gastric Cancer
Authors: Fang Hongming , Zhou Yujuan , Bai Xue , Che Wanlin , Zhang Wenxuan , Zhang Danying , Chen Qingmei , Duan Wei , Nie Guochao , Hou Yingchun
Published: September 2024

Background/Objectives: Gastric cancer (GC) is a globally frequent cancer, in particular leading in mortality caused by digestive tract cancers in China. Vascular endothelial growth factor A (VEGFA) is excessively expressed in cancers including GC; its involvement in GC development, particularly in multidrug resistance (MDR), and the signal route it affects in GC remain unknown. To explore the roles VEGFA plays during progression and MDR formation in GC, we studied its function in a VEGFA-deleted GC cell platform. Methods: We initially assessed the importance of VEGFA in GC and MDR using database analysis. Then, using CCK8, wound healing, transwell, scanning electron microscopy, immunofluorescence, flow cytometry, and other techniques, the alterations in tumor malignancy-connected cell behaviors and microstructures were photographed and evaluated in a VEGFA-gene-deleted GC cell line (VEGFA−/−SGC7901). Finally, the mechanism of VEGFA in GC progression and MDR was examined by Western blot. Results: Database analysis revealed a strong correlation between high VEGFA expression and a poor prognosis for GC. The results showed that VEGFA deletion reduced GC cell proliferation and motility and altered microstructures important for motility, such as the depolymerized cytoskeleton. VEGFA deletion inhibited the growth of pseudopodia/filopodia and suppressed the epithelial–mesenchymal transition (EMT). The occurrence of MDR is induced by overactivation of the MAPK-AKT and TGFβ signaling pathways, while PTEN inhibits these pathways. Conclusions: All findings suggested that VEGFA acts as a cancer enhancer and MDR inducer in GC via the MAPK-AKT/PTEN/TGFβ signal pathway.
De Novo Genome Assembly and Phylogenetic Analysis of Cirsium nipponicum
Authors: Choi Bae Young , Kim Jaewook , Park Hyeonseon , Kim Jincheol , Han Seahee , Jo Ick-Hyun , Shim Donghwan
Published: September 2024

Background: Cirsium nipponicum, a pharmaceutically valuable plant from the Asteraceae family, has been utilized for over 2000 years. Unlike other thistles, it is native to East Asia and found exclusively on Ulleung Island on the Korea Peninsula. Despite its significance, the genome information of C. nipponicum has remained unclear. Methods: In this study, we assembled the genome of C. nipponicum using both short reads from Illumina sequencing and long reads from Nanopore sequencing. Results: The assembled genome is 929.4 Mb in size with an N50 length of 0.7 Mb, covering 95.1% of BUSCO core groups listed in edicots_odb10. Repeat sequences accounted for 70.94% of the assembled genome. We curated 31,263 protein-coding genes, of which 28,752 were functionally annotated using public databases. Phylogenetic analysis of 11 plant species using single-copy orthologs revealed that C. nipponicum diverged from Cynara cardunculus approximately 15.9 million years ago. Gene family evolutionary analysis revealed significant expansion and contraction in genes involved in abscisic acid biosynthesis, late endosome to vacuole transport, response to nitrate, and abaxial cell fate specification. Conclusions: This study provides a reference genome of C. nipponicum, enhancing our understanding of its genetic background and facilitating an exploration of genetic resources for beneficial phytochemicals.
Exceptional Cluster of Simultaneous Shallow Landslides in Rwanda: Context, Triggering Factors, and Potential Warnings
Authors: Byiringiro Fils-Vainqueur , Jolivet Marc , Dauteuil Olivier , Arvor Damien , Hitimana Niyotwambaza Christine
Published: September 2024

Rwanda, in eastern tropical Africa, is a small, densely populated country where climatic disasters are often the cause of considerable damage and deaths. Landslides are among the most frequent hazards, linked to the country’s peculiar configuration including high relief with steep slopes, humid tropical climate with heavy rainfall, intense deforestation over the past 60 years, and extensive use of the soil for agriculture. The Karongi region, in the west-central part of the country, was affected by an exceptional cluster of more than 700 landslides during a single night (6–7 May 2018) over an area of 100 km2. We analyse the causes of this spectacular event based on field geological and geomorphology investigation and CHIRPS and ERA5-Land climate data. We demonstrate that (1) the notably steep slopes favoured soil instability; (2) the layered soil and especially the gravelly, porous C horizon allowed water storage and served as a detachment level for the landslides; (3) relatively low intensity, almost continuous rainfall over the previous two months lead to soil water-logging; and (4) acoustic waves from thunder or mechanical shaking by strong wind destabilized the water-logged soil through thixotropy triggering the landslides. This analysis should serve as a guide for forecasting landslide-triggering conditions in Rwanda.
A Methodology to Evaluate the Horizontal Earth Pressure Acting on Circular Shafts Based on Its Lateral Displacements
Authors: Pedro António M. G.
Published: September 2024

One of the most common solutions to access the underground is through the construction of circular shafts. At a preliminary design stage, analytical expressions are often used to estimate the horizontal earth pressure acting on the lining. However, most of these solutions are based on active state conditions and do not consider the restrictions imposed on the shaft lateral displacements by the rigidity of its lining or by the construction method employed. To overcome this limitation, a new methodology to account for the shaft lateral displacements in the determination of the horizontal earth pressure acting on circular shafts is developed and validated against the results of relevant physical scale models. The obtained results show good agreement with the measured data, adequately reproducing the reduction in the horizontal earth pressure from its initial value to an active state condition with an increase in the shaft lateral displacement. Following this approach, more realistic predictions of the earth pressure acting on the lining of circular shafts can be performed.
Static and Dynamic Cone Penetrometer Tests for Babolsar Sand Parameters via Physical Modeling
Authors: Eslami Abolfazl , Nobahar Masoud , Esmailzade Mohammad
Published: September 2024

Field tests are the most suitable method to determine geotechnical parameters. Owing to some restrictions in field tests, physical modeling has been widely accepted as a proper method to define mathematical correlations among geotechnical parameters. This study investigates correlations between parameters derived from cone penetrometer tests. The tests were performed in a cylindrical chamber with a height and diameter of 1000 mm to minimize the boundary effect. Coastal poorly graded sand sampled from the Babolsar region, adjacent to the Caspian Sea, was used. Some correlations among geotechnical parameters, including cone resistance, dynamic cone resistance, dynamic penetration index, modulus of elasticity, internal friction angle, and relative density, are presented. All correlations were categorized into three main categories: soil stiffness, penetration strength, and geotechnical parameters. The results had reasonable accuracy and precision. The average R2 value of the obtained results was approximately 94. The investigations into the inherent CPT also indicated that the strength parameter had more accuracy than stiffness and other sand parameters. Specifically, the R2 value for the correlation between the results of various penetration tests, considered strength parameters, averaged 97. In contrast, the R2 value for the correlation between the elasticity modulus and cone penetration test results was 86.
Impact of Probiotics and Prebiotics on Gut Microbiome and Hormonal Regulation
Authors: Basnet Jelina , Eissa Manar A. , Yanes Cardozo Licy L. , Romero Damian G. , Rezq Samar
Published: September 2024

The gut microbiome plays a crucial role in human health by influencing various physiological functions through complex interactions with the endocrine system. These interactions involve the production of metabolites, signaling molecules, and direct communication with endocrine cells, which modulate hormone secretion and activity. As a result, the microbiome can exert neuroendocrine effects and contribute to metabolic regulation, adiposity, and appetite control. Additionally, the gut microbiome influences reproductive health by altering levels of sex hormones such as estrogen and testosterone, potentially contributing to conditions like polycystic ovary syndrome (PCOS) and hypogonadism. Given these roles, targeting the gut microbiome offers researchers and clinicians novel opportunities to improve overall health and well-being. Probiotics, such as Lactobacillus and Bifidobacterium, are live beneficial microbes that help maintain gut health by balancing the microbiota. Prebiotics, non-digestible fibers, nourish these beneficial bacteria, promoting their growth and activity. When combined, probiotics and prebiotics form synbiotics, which work synergistically to enhance the gut microbiota balance and improve metabolic, immune, and hormonal health. This integrated approach shows promising potential for managing conditions related to hormonal imbalances, though further research is needed to fully understand their specific mechanisms and therapeutic potential.
New Insights into the Materials and Painting Techniques of Ancient Wall Paintings from the Roman Province of Dacia: A Minimally Invasive Multi-Method Approach
Authors: Cortea Ioana Maria , Ghervase Luminița , Ratoiu Lucian , Țentea Ovidiu , Dinu Monica
Published: September 2024

A group of wall painting fragments discovered at Ulpia Traiana Sarmizegetusa, an important Roman archeological site located in the former Roman province of Dacia (Romania), have been investigated with the aim of defining the material composition of their pictorial layers and exploring the pictorial technology used. In order to preserve the integrity of the murals and minimize sampling, an array of non- and micro-invasive techniques has been employed, including X-ray fluorescence, laser-induced breakdown spectroscopy, Fourier transform infrared spectroscopy, and hyperspectral imaging. In accordance with previous studies, the identified color palette was mainly based on iron-rich earth pigments (red and yellow ochres, green earth) and carbon-based blacks (soot/charcoal, bone black). Egyptian blue, lazurite, some lead-based pigments, and potentially indigo were also identified (in complex mixtures) on the uppermost paint layers, typically applied a secco over the a fresco background. The presence of expensive pigments and the existence of a red preparatory drawing, documented for the first time in the region, indicate that the original wall paintings had elaborate schemes and, secondly, reflect the patron’s wealth and social status. Hyperspectral imaging was able to retrieve some faded paint layers in certain cases, helping to recover lost decorative details, an indicator of a more complex polychromy compared to what we see today. The obtained results add important contributions to the limited corpus of data regarding the technical know-how of decorative polychrome painting on plaster found in Roman archeological sites in Romania.
Tradition in Action-Traditional Costume Innovations
Authors: Portelli Lorraine , Arvanitidou Zoi , McSweeney Kathryn , Räisänen Riikka
Published: September 2024

Traditional costumes and crafts are a basic form and element of local culture and a vital pathway for perpetuating traditional art and design culture. They are an artistic form of historical and cultural significance. This paper focuses on three traditional costumes from Malta, Ireland, and Finland. The għonnella, worn by Maltese women of different social classes, consisted of a voluminous cape-like covering reinforced with whalebone and cardboard and was worn over the head and shoulders, reaching ankle length. Irish costumes were adorned with beautiful Irish lace, crochet, and embroidery. Celtic embroidery was added to clothing to develop a distinctive Irish dress style during the great cultural revival of the early 20th century. The Karelian costume from Finland was constructed using wool and linen. Ladies in Karelia wore handcrafted, highly embroidered gowns, and traditions were passed down from older ladies, including mothers and grandmothers. These costumes were collected in the late nineteenth and early twentieth centuries when Finnish Karelia was known as ‘The Old Finland’. This paper delves into the origins of these costumes and how social and cultural events, with their intriguing influence, shaped their styles, features, colors, and fabrics.
Juglans regia as Urban Trees: Genetic Diversity and Walnut Kernel Quality Assessment
Authors: Tenche-Constantinescu Alina-Maria , Lalescu Dacian Virgil , Popescu Sorina , Sarac Ioan , Petolescu Cerasela , Camen Dorin , Horablaga Adina , Popescu Cosmin Alin , Herbei Mihai Valentin , Dragomir Lucian , Popescu George , Iordănescu Olimpia Alina , Becherescu Alexandra , Onisan Emilian
Published: September 2024

Juglans regia L. is an edible fruit tree cultivated worldwide for its fruits and wood and as an urban tree. Globally, there is growing concern for preserving the genetic diversity of trees with high economic and ecological value. This study investigates the genetic diversity of J. regia in urban landscapes and assesses the quality of its walnut kernels as a local food product. An inventory of 150 trees from five populations in public green spaces in Lugoj, Caransebeș and Jupa, as well as two semi-natural hilly ecosystems in the Banat Region, was conducted. Molecular analyses showed that Directed Amplification of Minisatellite-region DNA (DAMD) markers were more effective than Start Codon Targeted (SCoT) markers, with a higher average polymorphism of 56.26%, compared to 49.44%. DAMD07 achieved 100% polymorphism and DAMD05 showed a strong balance between P.I.C. (0.35) and polymorphism (54.54%). Chemical analysis revealed the following contents in walnut kernels: protein (12.81% to 16.80%), lipids (60.39% to 69.08%), total polyphenols (5484.66 to 10,788.4 mg GAE/kg), copper (3.655 to 8.532 mg/kg), manganese (14.408 to 28.618 mg/kg), zinc (19.813 to 46.583 mg/kg), lead (1.204 to 2.27 mg/kg) and cadmium (0.03451 to 0.08065 mg/kg). These findings are critical for conservation efforts, urban forestry management and ensuring the quality and safety of walnut products derived from J. regia.
Molecular and Physiological Responses of Toona ciliata to Simulated Drought Stress
Authors: Yang Linxiang , Zhao Peixian , Song Xiaobo , Ma Yongpeng , Fan Linyuan , Xie Meng , Song Zhilin , Zhang Xuexing , Ma Hong
Published: September 2024

Drought stress, as one of the most common environmental factors, seriously affects seed- ling establishment as well as plant growth and productivity. The growth of Toona ciliata is constrained by soil moisture deficit, and drought stress can reduce its productivity and limit its suitable growing environment. To explore the molecular mechanism of Toona ciliata responding to drought stress, leaves of two-year-old Toona ciliata seedlings were used as experimental materials for transcriptome sequencing and physiological index measurements. Under drought stress, the contents of Chl, MDA, POD, SP, SS, and RWC all change differently. We performed transcriptome sequencing, obtaining 4830 differential genes. The enrichment analysis indicates that the primary effects on the leaves of Toona ciliata under drought stress are related to photosynthesis and responses to plant hormone signal transduction. Transcription factor families associated with drought resistance include the NAC, WRKY, bZIP, bHLH, AP2-EREBP, C3H, GRAS, and FRAI transcription factor families. A weighted gene co-expression network analysis (WGCNA) analysis successfully identified 10 hub genes in response to drought stress in Toona ciliata leaves. Real-time quantitative PCR (RT-qPCR) validated the reliability of the transcriptomic data, and the analysis of its results showed a close correlation with the data obtained from RNA-seq. This study clarifies the transcriptional response of Toona ciliata to drought stress, contributing to the revelation of the molecular mechanisms of drought adaptation.
Investigating Pregnant Women’s Attitudes toward Herbal Remedies: A Cross-Sectional Study
Authors: Al-Tawalbeh Deniz , Hamdan Falastine , Al-Momani Eshraq , Atiyeh Huda , Mayyas Amal
Published: September 2024

Background: Herbal remedies play a significant role in daily life, regardless of region or ethnicity. While they offer various health benefits, they may also pose risks, including toxicity and undesirable side effects. Pregnant women, one of the most vulnerable populations, frequently use herbal remedies, often without informing their healthcare providers, which can lead to unforeseen consequences for both the mother and the fetus. Method: A total of 590 women participated in an online survey designed to assess demographic factors, awareness of herbal remedies during pregnancy, and the potential impact of these remedies on maternal and fetal health. Results: The survey revealed that 35.8% of the participants used herbal remedies during pregnancy. The most common reasons for their use were beliefs in their safety and family recommendations. Anise (Pimpinella anisum L.) was the most frequently used herb. Conclusions: The findings indicate that pregnant women generally have limited knowledge about herbal remedies and their potential risks. To mitigate this, it is essential to develop and disseminate comprehensive safety and efficacy guidelines. Both physicians and pregnant women should be well-informed to ensure the protection of maternal and fetal health.
Nanomedicine in Bladder Cancer Therapy
Authors: Winnicka Adrianna , Brzeszczyńska Joanna , Saluk Joanna , Wigner-Jeziorska Paulina
Published: September 2024

Bladder cancer (BC) is one of the most common malignant neoplasms of the genitourinary system. Traditional BC therapies include chemotherapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multidrug resistance pose serious challenges to the benefits of BC therapies. Consequently, current studies focus on the search for new therapeutic solutions. In recent years, there has been a growing interest in using nanotechnology in the treatment of both non-invasive (NMIBC) and invasive bladder cancer (MIBC). Nanotechnology is based on the use of both organic molecules (chitosan, liposomes) and inorganic molecules (superparamagnetic iron oxide nanoparticles) as carriers of active substances. The main aim of such molecules is the targeted transport and prolonged retention of the drug in the target tissue, which increases the therapeutic efficacy of the active substance. This review discusses the numerous types of nanoparticles (including chitosan, polymeric nanoparticles, liposomes, and protein nanoparticles), targeting mechanisms, and approved nanotherapeutics with oncological implications in cancer treatment. We also present nanoformulation applications in phototherapy, gene therapy, and immunotherapy. Moreover, we summarise the current perspectives, advantages, and challenges in clinical translation.
Update on Biomarkers of Chronic Inflammatory Processes Underlying Diabetic Neuropathy
Authors: Stoian Adina , Muntean Carmen , Babă Dragoș-Florin , Manea Andrei , Dénes Lóránd , Simon-Szabó Zsuzsánna , Kosovski Irina Bianca , Nemes-Nagy Enikő , Gliga Florina Ioana , Stoian Mircea
Published: September 2024

There is an increasing prevalence of diabetes mellitus (DM), particularly type 2 DM (T2DM), and its associated complications. T2DM is linked to insulin resistance, chronic inflammation, and oxidative stress, which can lead to both macrovascular and microvascular complications, including peripheral diabetic neuropathy (PDN). Inflammatory processes play a key role in the development and progression of T2DM and its complications, with specific markers like C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor (TNF)-α being associated with increased risk. Other key inflammatory markers such as nuclear factor kappa B (NF-κB) are activated under hyperglycemic and oxidative stress conditions and contribute to the aggravation of PDN by regulating inflammatory gene expression and enhancing endothelial dysfunction. Other important roles in the inflammatory processes are played by Toll-like receptors (TLRs), caveolin 1 (CAV1), and monocyte chemoattractant protein 1 (MCP1). There is a relationship between vitamin D deficiency and PDN, highlighting the critical role of vitamin D in regulating inflammation and immune responses. The involvement of macrophages in PDN is also suspected, emphasizing their role in chronic inflammation and nerve damage in diabetic patients. Vitamin D supplementation has been found to reduce neuropathy severity, decrease inflammatory markers, and improve glycemic control. These findings suggest that addressing vitamin D deficiency could offer therapeutic benefits for PDN. These molecular pathways are critical in understanding the pathogenesis of DM complications and may offer potential biomarkers or therapeutic targets including anti-inflammatory treatments, vitamin D supplementation, macrophage phenotype modulation, and lifestyle modifications, aimed at reducing inflammation and preventing PDN. Ongoing and more extensive clinical trials with the aim of investigating anti-inflammatory agents, TNF-α inhibitors, and antioxidants are needed to advance deeper into the understanding and treatment of painful diabetic neuropathy.
Npac Regulates Pre-mRNA Splicing in Mouse Embryonic Stem Cells
Authors: Qian Yiwei , Ye Ying , Zhang Wensheng , Wu Qiang
Published: September 2024

As a reader of tri-methylated lysine 36 on histone H3 (H3K36me3), Npac has been shown to have a significant role in gene transcription elongation. However, its potential implication in RNA splicing remains unknown. Here, we characterized the phenotypes of Npac knockout in mES cells. We discovered that loss of Npac disrupts pluripotency and identity in mESCs. We also found that Npac is associated with many cellular activities, including cell proliferation, differentiation, and transcription regulation. Notably, we uncovered that Npac is associated with RNA splicing machinery. Furthermore, we found that Npac regulates alternative splicing through its interaction with the splicing factors, including Srsf1. Our research thus highlights the important role of Npac in maintaining ESC identity through the regulation of pre-mRNA splicing.
Mass Spectrometry Analysis of Neurotransmitter Shifting during Neurogenesis and Neurodegeneration of PC12 Cells
Authors: Jao Yu-Ning , Chao Yu-Jen , Chan Jui-Fen , Hsu Yuan-Hao Howard
Published: September 2024

Parkinson’s disease (PD) affects movement; however, most patients with PD also develop nonmotor symptoms, such as hyposmia, sleep disorder, and depression. Dopamine levels in the brain have a critical influence on movement control, but other neurotransmitters are also involved in the progression of PD. This study analyzed the fluctuation of neurotransmitters in PC12 cells during neurogenesis and neurodegeneration by performing mass spectrometry. We found that the dopaminergic metabolism pathway of PC12 cells developed vigorously during the neuron differentiation process and that the neurotransmitters were metabolized into 3-methoxytyramine, which was released from the cells. The regulation of the intracellular and extracellular concentrations of adenosine indicated that adenine nucleotides were actively utilized in neural differentiation. Moreover, we exposed the differentiated PC12 cells to rotenone, which is a suitable material for modeling PD. The cells exposed to rotenone in the early stage of differentiation exhibited stimulated serotoninergic metabolism, and the contents of the serotoninergic neurotransmitters returned to their normal levels in the late stage of differentiation. Interestingly, the nondifferentiated cells can resist the toxicant rotenone and produce normal dopaminergic metabolites. However, when differentiated neuron cells were exposed to rotenone, they were seriously damaged, leading to a failure to produce dopaminergic neurotransmitters. In the low-dosage damage process, the amino acids that functioned as dopaminergic pathway precursors could not be absorbed by the cells, and dopamine and L-dopa were secreted and unable to be reuptaken to trigger the cell damage.
Selective Effect of DNA N6-Methyladenosine Modification on Transcriptional Genetic Variations in East Asian Samples
Authors: Luan Meiwei , Chen Kaining , Zhao Wenwen , Tang Minqiang , Wang Lingxia , Liu Shoubai , Zhu Linan , Xie Shangqian
Published: September 2024

Genetic variations and DNA modification are two common dominant factors ubiquitous across the entire human genome and induce human disease, especially through static genetic variations in DNA or RNA that cause human genetic diseases. DNA N6-methyladenosine (6mA) methylation, as a new epigenetic modification mark, has been widely studied for regulatory biological processes in humans. However, the effect of DNA modification on dynamic transcriptional genetic variations from DNA to RNA has rarely been reported. Here, we identified DNA, RNA and transcriptional genetic variations from Illumina short-read sequencing data in East Asian samples (HX1 and AK1) and detected global DNA 6mA modification using single-molecule, real-time sequencing (SMRT) data. We decoded the effects of DNA 6mA modification on transcriptional genetic variations in East Asian samples and the results were extensively verified in the HeLa cell line. DNA 6mA modification had a stabilized distribution in the East Asian samples and the methylated genes were less likely to mutate than the non-methylated genes. For methylated genes, the 6mA density was positively correlated with the number of variations. DNA 6mA modification had a selective effect on transcriptional genetic variations from DNA to RNA, in which the dynamic transcriptional variations of heterozygous (0/1 to 0/1) and homozygous (1/1 to 1/1) were significantly affected by 6mA modification. The effect of DNA methylation on transcriptional genetic variations provides new insights into the influencing factors of DNA to RNA transcriptional regulation in the central doctrine of molecular biology.
Basic Guide for Approaching Drug Delivery with Extracellular Vesicles
Authors: Brezgin Sergey , Danilik Oleg , Yudaeva Alexandra , Kachanov Artyom , Kostyusheva Anastasiya , Karandashov Ivan , Ponomareva Natalia , Zamyatnin Andrey A. , Parodi Alessandro , Chulanov Vladimir , Kostyushev Dmitry
Published: September 2024

Extracellular vesicles (EVs) are natural carriers of biomolecules that play a crucial role in cell-to-cell communication and tissue homeostasis under normal and pathological conditions, including inflammatory diseases and cancer. Since the discovery of the pro-regenerative and immune-modulating properties of EVs, EV-based therapeutics have entered clinical trials for conditions such as myocardial infarction and autoimmune diseases, among others. Due to their unique advantages—such as superior bioavailability, substantial packaging capacity, and the ability to traverse biological barriers—EVs are regarded as a promising platform for targeted drug delivery. However, achieving a sufficient accumulation of therapeutic agents at the target site necessitates a larger quantity of EVs per dose compared to using EVs as standalone drugs. This challenge can be addressed by administering larger doses of EVs, increasing the drug dosage per administration, or enhancing the selective accumulation of EVs at target cells. In this review, we will discuss methods to improve the isolation and purification of EVs, approaches to enhance cargo packaging—including proteins, RNAs, and small-molecule drugs—and technologies for displaying targeting ligands on the surface of EVs to facilitate improved targeting. Ultimately, this guide can be applied to the development of novel classes of EV-based therapeutics and to overcoming existing technological challenges.
Molecular Mechanisms for Regulating Stomatal Formation across Diverse Plant Species
Authors: Zhou Wenqi , Liu Jieshan , Wang Wenjin , Li Yongsheng , Ma Zixu , He Haijun , Wang Xiaojuan , Lian Xiaorong , Dong Xiaoyun , Zhao Xiaoqiang , Zhou Yuqian
Published: September 2024

Plant stomata play a crucial role in photosynthesis by regulating transpiration and gas exchange. Meanwhile, environmental cues can also affect the formation of stomata. Stomatal formation, therefore, is optimized for the survival and growth of the plant despite variable environmental conditions. To adapt to environmental conditions, plants open and close stomatal pores and even regulate the number of stomata that develop on the epidermis. There are great differences in the leaf structure and developmental origin of the cell in the leaf between Arabidopsis and grass plants. These differences affect the fine regulation of stomatal formation due to different plant species. In this paper, a comprehensive overview of stomatal formation and the molecular networks and genetic mechanisms regulating the polar division and cell fate of stomatal progenitor cells in dicotyledonous plants such as Arabidopsis and Poaceae plants such as Oryza sativa and Zea mays is provided. The processes of stomatal formation mediated by plant hormones and environmental factors are summarized, and a model of stomatal formation in plants based on the regulation of multiple signaling pathways is outlined. These results contribute to a better understanding of the mechanisms of stomatal formation and epidermal morphogenesis in plants and provide a valuable theoretical basis and gene resources for improving crop resilience and yield traits.
Genome-Guided Identification of Surfactin-Producing Bacillus halotolerans AQ11M9 with Anti-Candida auris Potential
Authors: Borgio J. Francis , Alhujaily Rahaf , Alfaraj Aqeelah Salman , Alabdullah Maryam Jawad , Alaqeel Rawan Khalid , Kaabi Ayidah , Alquwaie Rahaf , Alhur Norah F. , AlJindan Reem , Almofty Sarah , Almohazey Dana , Natarajan Anandakumar , Dhas Tharmathass Stalin , AbdulAzeez Sayed , Almandil Noor B.
Published: September 2024

The emergence of multidrug-resistant fungi Candida auris is a worldwide health crisis connected with high rates of mortality. There is a critical need to find novel and unique antifungal compounds for treating infections of multidrug-resistant fungi such as C. auris. This study aimed to illustrate that biosynthetic gene clusters in native bacterial isolates are able to produce antifungal compounds against the multidrug-resistant fungus C. auris. It was successfully achieved using large-scale antifungal activity screening, cytotoxicity analysis, and whole genome sequencing integrated with genome mining-guided analysis and liquid chromatography–mass spectrometry (LC/MS). A list of possible gene candidates was initially identified with genome mining methods to predict secondary metabolite gene clusters of antifungal-compound-producing bacteria. Then, gene clusters present in the antifungal-compound-producing bacteria were identified and aligned with the reference genome using comparative genomic approaches. Bacillus halotolerans AQ11M9 was identified through large-scale antifungal activity screening as a natural compound-producer against multidrug-resistant C. auris, while it was nontoxic to normal human skin fibroblast cells (confirmed using a cell viability assay). The genome (4,197,347 bp) of B. halotolerans AQ11M9 with 2931 predicted genes was first mined for detecting and characterizing biosynthetic gene clusters, which revealed 10 candidate regions with antifungal activity. Clusters of AQ11M9 encoded non-ribosomal peptide synthase (NRPS) (bacilysin, bacillibactin, paenibactin, surfactin, plipastin, and fengycin) and polyketide (macrobrevin). The presence of gene clusters with anti-C. auris activity, and surfactin identified through LC/MS, from AQ11M9 suggests the potential of utilizing it as a source for a novel and powerful anti-C. auris compound.
Effects of Nitrogen Deficiency on the Photosynthesis, Chlorophyll a Fluorescence, Antioxidant System, and Sulfur Compounds in Oryza sativa
Authors: Chen Ling-Hua , Xu Ming , Cheng Zuxin , Yang Lin-Tong
Published: September 2024

Decreasing nitrogen (N) supply affected the normal growth of Oryza sativa (O. sativa) seedlings, reducing CO2 assimilation, stomatal conductance (gs), the contents of chlorophylls (Chl) and the ratio of Chl a/Chl b, but increasing the intercellular CO2 concentration. Polyphasic chlorophyll a fluorescence transient and relative fluorescence parameters (JIP test) results indicated that N deficiency increased Fo, but decreased the maximum quantum yield of primary photochemistry (Fv/Fm) and the maximum of the IPphase, implying that N-limiting condition impaired the whole photo electron transport chain from the donor side of photosystem II (PSII) to the end acceptor side of PSI in O. sativa. N deficiency enhanced the activities of the antioxidant enzymes, such as ascorbate peroxidase (APX), guaiacol peroxidase (GuPX), dehydro–ascorbate reductase (DHAR), superoxide dismutase (SOD), glutathione peroxidase (GlPX), glutathione reductase (GR), glutathione S-transferase (GST) and O-acetylserine (thiol) lyase (OASTL), and the contents of antioxidant compounds including reduced glutathione (GSH), total glutathione (GSH+GSSG) and non-protein thiol compounds in O. sativa leaves. In contrast, the enhanced activities of catalase (CAT), DHAR, GR, GST and OASTL, the enhanced ASC–GSH cycle and content of sulfur-containing compounds might provide protective roles against oxidative stress in O. sativa roots under N-limiting conditions. Quantitative real-time PCR (qRT-PCR) analysis indicated that 70% of the enzymes have a consistence between the gene expression pattern and the dynamic of enzyme activity in O. sativa leaves under different N supplies, whereas only 60% of the enzymes have a consistence in O. sativa roots. Our results suggested that the antioxidant system and sulfur metabolism take part in the response of N limiting condition in O. sativa, and this response was different between leaves and roots. Future work should focus on the responsive mechanisms underlying the metabolism of sulfur-containing compounds in O. sativa under nutrient deficient especially N-limiting conditions.
Identification of a Novel Gene MtbZIP60 as a Negative Regulator of Leaf Senescence through Transcriptome Analysis in Medicago truncatula
Authors: Xing Jiayu , Wang Jialan , Cao Jianuo , Li Ke , Meng Xiao , Wen Jiangqi , Mysore Kirankumar S. , Wang Geng , Zhou Chunjiang , Yin Pengcheng
Published: September 2024

Leaves are the primary harvest portion in forage crops such as alfalfa (Medicago sativa). Delaying leaf senescence is an effective strategy to improve forage biomass production and quality. In this study, we employed transcriptome sequencing to analyze the transcriptional changes and identify key senescence-associated genes under age-dependent leaf senescence in Medicago truncatula, a legume forage model plant. Through comparing the obtained expression data at different time points, we obtained 1057 differentially expressed genes, with 108 consistently up-regulated genes across leaf growth and senescence. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the 108 SAGs mainly related to protein processing, nitrogen metabolism, amino acid metabolism, RNA degradation and plant hormone signal transduction. Among the 108 SAGs, seven transcription factors were identified in which a novel bZIP transcription factor MtbZIP60 was proved to inhibit leaf senescence. MtbZIP60 encodes a nuclear-localized protein and possesses transactivation activity. Further study demonstrated MtbZIP60 could associate with MtWRKY40, both of which exhibited an up-regulated expression pattern during leaf senescence, indicating their crucial roles in the regulation of leaf senescence. Our findings help elucidate the molecular mechanisms of leaf senescence in M. truncatula and provide candidates for the genetic improvement of forage crops, with a focus on regulating leaf senescence.
Knockdown of Adenosine 5′-Triphosphate-Dependent Caseinolytic Protease Proteolytic Subunit 6 Enhances Aluminum Tolerance in Peanut Plants (Arachis hypogea L.)
Authors: Shi Yusun , Zhang Dayue , Liang Ronghua , Xiao Dong , Wang Aiqin , He Longfei , Zhan Jie
Published: September 2024

Aluminum (Al3+) toxicity in acidic soils reduces root growth and can lead to a considerable reduction in peanut plants (Arachis hypogea L.). The caseinolytic protease (Clp) system plays the key role in abiotic stress response. However, it is still unknown whether it is involved in peanut response to Al3+ stress. The results from this study showed that Adenosine 5′-triphosphate (ATP)-dependent caseinolytic protease proteolytic subunit 6 (AhClpP6) in peanut plants was involved in the Al3 stress response through its effects on leaf photosynthesis. The AhClpP6 expression levels in the leaf and stem significantly increased with the Al3+ treatment times. Knockdown AhClpP6 peanut lines accumulated significantly more Al3+ when exposed to Al3+ stress, which reduced leaf photosynthesis. Furthermore, in response to Al3+ treatment, knockdown of AhClpP6 resulted in a flattened shape of chloroplasts, disordered and flattened thylakoid, and accumulating more starch grains than those of the wild-type (WT) peanut lines. Taken together, our results suggest that AhClpP6 regulates Al3+ tolerance by maintaining chloroplast integrity and enhancing photosynthesis.
Exploring Senolytic and Senomorphic Properties of Medicinal Plants for Anti-Aging Therapies
Authors: Imb Monika , Véghelyi Zsolt , Maurer Michael , Kühnel Harald
Published: September 2024

Senolytic and senomorphic therapies have gained more and more attention in the last decade. This kind of therapy is based on the killing of cellular senescent cells without harming the “normal” cells. Aging is not a disease. Clinical studies on healthy people will be difficult to conduct. Therefore, one possibility is to draw on the large repertoire of medicinal plants and use their senolytic properties to provide mild anti-aging therapies. Chamomile, goldenrod, reishi, and green tea were tested for their ability to trigger senolysis. Quercetin was used as control substance. Cellular senescence was induced with 25 µM etoposide in human dermal fibroblasts and established for at least 14 days. The plant extracts were tested for their antioxidant potential (DPPH assay) and their polyphenol content. Senolysis was determined by presto blue assay of young and etoposide-induced senescent cells, and SA-β-Gal assays were also performed. The senomorphic properties of the plants were investigated using IL-6 ELISA and qPCR. It turned out that chamomile triggers a kind of cytokine storm and causes the cytokine values in the ELISA and in the qPCR to rise extremely, and other senescence-associated phenotype (SASP) markers were also elevated. Goldenrod and quercetin tend to have a senolytic and senomorphic effect, respectively. Regarding the senolytic and senomorphic properties of herbs, we found that all tested herbs can have a senolytic effect, and a senomorphic effect of quercetin has also been discovered. With regard to the effect of chamomile, however, we can say that seemingly harmless tea products may have harmful effects, especially in combination with chemotherapy, at least in cell culture experiments. Nevertheless, inflammation is a double-bladed mechanism with positive effects, for example, in healing, but also known negative effects.
Influence of Primary Light Exposure on the Morphophysiological Characteristics and Phenolic Compounds Accumulation of a Tea Callus Culture (Camellia sinensis L.)
Authors: Zubova Maria Y. , Goncharuk Evgenia A. , Nechaeva Tatiana L. , Aksenova Maria A. , Zaitsev Georgiy P. , Katanskaya Vera M. , Kazantseva Varvara V. , Zagoskina Natalia V.
Published: September 2024

Tea plant calli (Camellia sinensis L.) are characterized by the accumulation of various phenolic compounds (PC)—substances with high antioxidant activity. However, there is still no clarity on the response of tea cells to light exposure of varying intensity. The purpose of the research was to study tea callus cultures grown under the influence of primary exposure to different light intensities (50, 75, and 100 µmol·m−2·s−1). The cultures’ growth, morphology, content of malondialdehyde and photosynthetic pigments (chlorophyll a and b), accumulation of various PC, including phenylpropanoids and flavanols, and the composition of catechins were analyzed. Primary exposure to different light intensities led to the formation of chloroplasts in tea calli, which was more pronounced at 100 µmol·m−2·s−1. Significant similarity in the growth dynamics of cultures, accumulation of pigments, and content of malondialdehyde and various phenolics in tea calli grown at light intensities of 50 and 75 µmol·m−2·s−1 has been established, which is not typical for calli grown at 100 µmol·m−2·s−1. According to data collected using high-performance liquid chromatography, (+)-catechin, (−)-epicatechin, epigallocatechin, gallocatechin gallate, epicatechin gallate, and epigallocatechin gallate were the main components of the tea callus culture’s phenolic complex. Its content changed under the influence of primary exposure to light, reaching the greatest accumulation in the final stages of growth, and depended on the light intensity. The data obtained indicate changes in the morphophysiological and biochemical characteristics of tea callus cultures, including the accumulation of PC and their individual representatives under primary exposure to light exposure of varying intensity, which is most pronounced at its highest values (100 µmol·m−2·s−1).
Genome-Wide Characterization of the INDETERMINATE DOMAIN (IDD) Zinc Finger Gene Family in Solanum lycopersicum and the Functional Analysis of SlIDD15 in Shoot Gravitropism
Authors: Wu Huan , Liu Mingli , Fang Yuqi , Yang Jing , Xie Xiaoting , Zhang Hailong , Zhou Dian , Zhou Yueqiong , He Yexin , Chen Jianghua , Bai Quanzi
Published: September 2024

The plant-specific IDD transcription factors (TFs) are vital for regulating plant growth and developmental processes. However, the characteristics and biological roles of the IDD gene family in tomato (Solanum lycopersicum) are still largely unexplored. In this study, 17 SlIDD genes were identified in the tomato genome and classified into seven subgroups according to the evolutionary relationships of IDD proteins. Analysis of exon–intron structures and conserved motifs reflected the evolutionary conservation of SlIDDs in tomato. Collinearity analysis revealed that segmental duplication promoted the expansion of the SlIDD family. Ka/Ks analysis indicated that SlIDD gene orthologs experienced predominantly purifying selection throughout evolution. The analysis of cis-acting elements revealed that the promoters of SlIDD genes contain numerous elements associated with light, plant hormones, and abiotic stresses. The RNA-seq data and qRT-PCR experimental results showed that the SlIDD genes exhibited tissue-specific expression. Additionally, Group A members from Arabidopsis thaliana and rice are known to play a role in regulating plant shoot gravitropism. QRT-PCR analysis confirmed that the expression level of SlIDD15 in Group A was high in the hypocotyls and stems. Subcellular localization demonstrated that the SlIDD15 protein was localized in the nucleus. Surprisingly, the loss-of-function of SlIDD15 by CRISPR/Cas9 gene editing technology did not display obvious gravitropic response defects, implying the existence of functional redundant factors within SlIDD15. Taken together, this study offers foundational insights into the tomato IDD gene family and serves as a valuable guide for exploring their molecular mechanisms in greater detail.