bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological and Transcriptomic Analysis of Citrus Fruit Segment Drying under Facility-Forcing Cultivation
Authors: Jin Longfei , Wen Mingxia , Liu Feng , Huang Bei , Wang Peng
Published: July 2024

Facility-forcing cultivation could effectively improve the quality of ‘Beni Madonna’ citrus (Citrus nankao × C. amakusa) and advance the ripening period. However, segment drying (KS) before harvest caused fruit quality deterioration and commodity value loss. In this research, we investigated the physiological and molecular characteristics involved in citrus segment drying under facility-forcing cultivation. The juice yield, sugar, acid, vitamin C, and lignin contents in KS fruits were significantly decreased, and the contents of pectin and cellulose were significantly increased. The relative contents of abscisic acid and abscisic acid glucosyl ester in KS fruits were significantly decreased. A total of 1215 differentially expressed genes (DEGs) were screened by transcriptome sequencing. DEGs were significantly enriched in water metabolism, sugar metabolism, transportation, cell wall and phenylpropanoid biosynthesis, and plant hormone signal transduction. The decrease in water absorption and sugar synthesis, the increase of pectin and cellulose synthesis, and the decrease in ABA accumulation may be the main reasons that cause citrus fruit segments to dry under facility-forcing cultivation.
Effects of Selenate Application on Growth, Nutrient Bioaccumulation, and Bioactive Compounds in Broccoli (Brassica oleracea var. italica L.)
Authors: Poblaciones Maria J. , García-Latorre Carlos , Velazquez Rocio , Broadley Martin R.
Published: July 2024

The biofortification of edible crops with selenium (Se) is a common and effective strategy to address inadequate Se intake, which is suffered by millions of people worldwide. However, there is little information regarding the effects of this practice on crops belonging to the important Brassica family. To evaluate the efficacy of foliar Se application on broccoli, four treatments with varying Se concentrations were tested: 0%, 0.05%, 0.10%, and 0.15% (w/v), applied as sodium selenate during the early flowering stage. Although no overall effects on growth and biomass parameters were observed, the results indicate that the lowest Se dose (0.05-Se) was sufficient to notably increase Se concentration in the florets, even after boiling. Based on the increase to 14.2 mg Se kg−1 of dry matter in this broccoli fraction, it was estimated that consuming a 100-gram portion of boiled florets biofortified with 0.05% Se would provide approximately 140 µg of Se, which could be sufficient to potentially improve human selenium status, as previously documented. Moreover, the results obtained underscore how the application of this small dose was also adequate to reduce phytate concentration in the florets and to increase antioxidant and polyphenol concentrations, thereby improving the concentration and bioavailability of other essential nutrients, including Ca, Mg, Fe, and Zn, along with improving its quality as an antioxidant food.
Assessment of Heavy Metal Contamination and Health Risks in “Snow Cover–Soil Cover–Vegetation System” of Urban and Rural Gardens of an Industrial City in Kazakhstan
Authors: Faurat Alina , Azhayev Galymbek , Shupshibayev Kazbek , Akhmetov Kairat , Boribay Elmira , Abylkhassanov Talgat
Published: July 2024

This article investigates the extent of heavy metal pollution in both urban and rural gardens in Pavlodar, which cultivate potatoes and tomatoes. As a city of industrialization, Pavlodar is exposed to emissions from industrial enterprises, transport and stove heating. The city also has the highest incidence of environmental diseases among the population. This study examines the accumulation of heavy metals and metalloid in the snow, their migration into the soil and their accumulation in plants, and assesses the non-cancer and cancer health risks of consuming these vegetables. The results show that the concentrations of trace elements in the solid phase of snow decrease in the following order: Fe (26,000) > Mn (592.5) > Cr (371.3) > Zn (338.8) > Pb (161.9) > Cu (142.5) > Ni (30.9) > As (15.1) > Co (12.1) > Cd (2.6). In soils, the concentrations of elements decrease in the following order: Mn (22,125) > Fe (20,375) > Zn (246.9) > Cr (109.5) > Cu (39.3) > Pb (25.6) > Ni (22.4) > As (9) > Co (6.6) > Cd (0.2). In urban gardens, the snow pollution coefficient was the highest. In rural gardens, the contamination index varied from 0.3 (Cr) to 5.3 (Cd). Magnesium in the soil exceeds the maximum allowable concentration (MPC) by 28.6–35.7 times, and zinc by 1.6–10.9 times. Only zinc and copper exceed the MPC for vegetables. Nickel in potatoes exceeds MPC by a factor of 6 and in tomatoes by a factor of 4.4. The cobalt content in tomatoes exceeds the background value by 2.2 times, with a maximum value of 5.3 times. The risk assessment showed that the non-carcinogenic and carcinogenic risks associated with potato and tomato consumption were low. However, these risks are higher in urban areas than in rural areas.
Identification and Analysis of the Mechanism of Stem Mechanical Strength Enhancement for Maize Inbred Lines QY1
Authors: Yang Yumeng , Mu Jianing , Hao Xiaoning , Yang Kangkang , Cao Ziyu , Feng Jiping , Li Runhao , Zhang Ning , Zhou Gongke , Kong Yingzhen , Wang Dian
Published: July 2024

Enhancing stalk strength is a crucial strategy to reduce lodging. We identified a maize inbred line, QY1, with superior stalk mechanical strength. Comprehensive analyses of the microstructure, cell wall composition, and transcriptome of QY1 were performed to elucidate the underlying factors contributing to its increased strength. Notably, both the vascular bundle area and the thickness of the sclerenchyma cell walls in QY1 were significantly increased. Furthermore, analyses of cell wall components revealed a significant increase in cellulose content and a notable reduction in lignin content. RNA sequencing (RNA-seq) revealed changes in the expression of numerous genes involved in cell wall synthesis and modification, especially those encoding pectin methylesterase (PME). Variations in PME activity and the degree of methylesterification were noted. Additionally, glycolytic efficiency in QY1 was significantly enhanced. These findings indicate that QY1 could be a valuable resource for the development of maize varieties with enhanced stalk mechanical strength and for biofuel production.
Neuroprotective Effect of Clemastine Improved Oligodendrocyte Proliferation through the MAPK/ERK Pathway in a Neonatal Hypoxia Ischemia Rat Model
Authors: Bernis Maria E. , Hakvoort Charlotte , Nacarkucuk Efe , Burkard Hannah , Bremer Anna-Sophie , Zweyer Margit , Maes Elke , Grzelak Kora A. , Sabir Hemmen
Published: July 2024

Neonatal hypoxic-ischemic encephalopathy is the most common cause of long-term disability in term neonates, and white matter injury is the primary cause of cerebral palsy. Therapies that focus on the neuroprotection of myelination and oligodendrocyte proliferation could potentially ameliorate long-lasting neurological impairments after hypoxic-ischemic encephalopathy. Clemastine, a histamine H1 antagonist, has been shown to exert neuroprotective effects in multiple sclerosis and spinal cord injury by promoting oligodendrogenesis and re-myelination. In this study, we demonstrated the neuroprotective effects of clemastine in our rat model of neonatal hypoxic-ischemic brain injury. Animals received a single intraperitoneal injection of either vehicle or clemastine (10 mg/kg) for 6 consecutive days. Our results showed a significant reduction in white matter loss after treatment, with a clear effect of clemastine on oligodendrocytes, showing a significant increase in the number of Olig2+ cells. We characterized the MAPK/ERK pathway as a potential mechanistic pathway underlying the neuroprotective effects of clemastine. Altogether, our results demonstrate that clemastine is a potential compound for the treatment of hypoxic-ischemic encephalopathy, with a clear neuroprotective effect on white matter injury by promoting oligodendrogenesis.
Comparison of Natural Killer Cells Differentiated from Various Pluripotent Stem Cells
Authors: Han Jongsuk , Son Hyeongbin , Jung Daun , Kim Ki-Yeon , Jin Chaeyeon , Hwang Hyeonwook , Kang Soon-Suk , Mitalipov Shoukhrat , An Hee-Jung , Lee Yeonmi , Kang Eunju
Published: July 2024

Allogeneic natural killer (NK) cell therapy has been effective in treating cancer. Many studies have tested NK cell therapy using human pluripotent stem cells (hPSCs). However, the impacts of the origin of PSC-NK cells on competence are unclear. In this study, several types of hPSCs, including human-induced PSCs (hiPSCs) generated from CD34+, CD3−CD56+, and CD56− cells in umbilical cord blood (UCB), three lines of human embryonic stem cells (hESCs, ES-1. ES-2 and ES-3) and MHC I knockout (B2M-KO)-ESCs were used to differentiate into NK cells and their capacities were analyzed. All PSC types could differentiate into NK cells. Among the iPSC-derived NK cells (iPSC-NKs) and ESC-derived NK cells (ES-NKs), 34+ iPSCs and ES-3 had a higher growth rate and cytotoxicity, respectively, ES-3 also showed better efficacy than 34+ iPSCs. B2M-KO was similar to the wild type. These results suggest that the screening for differentiation of PSCs into NK cells prior to selecting the PSC lines for the development of NK cell immunotherapy is an essential process for universal allotransplantation, including the chimeric antigen receptor (CAR).
Bioenergetic and Inflammatory Alterations in Regressed and Non-Regressed Patients with Autism Spectrum Disorder
Authors: Gevezova Maria , Ivanov Zdravko , Pacheva Iliana , Timova Elena , Kazakova Maria , Kovacheva Eleonora , Ivanov Ivan , Sarafian Victoria
Published: July 2024

Autism spectrum disorder (ASD) is associated with multiple physiological abnormalities. Current laboratory and clinical evidence most commonly report mitochondrial dysfunction, oxidative stress, and immunological imbalance in almost every cell type of the body. The present work aims to evaluate oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and inflammation-related molecules such as Cyclooxygenase-2 (COX-2), chitinase 3-like protein 1 (YKL-40), Interleukin-1 beta (IL-1β), Interleukin-9 (IL-9) in ASD children with and without regression compared to healthy controls. Children with ASD (n = 56) and typically developing children (TDC, n = 12) aged 1.11 to 11 years were studied. Mitochondrial activity was examined in peripheral blood mononuclear cells (PBMCs) isolated from children with ASD and from the control group, using a metabolic analyzer. Gene and protein levels of IL-1β, IL-9, COX-2, and YKL-40 were investigated in parallel. Our results showed that PBMCs of the ASD subgroup of regressed patients (ASD R(+), n = 21) had a specific pattern of mitochondrial activity with significantly increased maximal respiration, respiratory spare capacity, and proton leak compared to the non-regressed group (ASD R(-), n = 35) and TDC. Furthermore, we found an imbalance in the studied proinflammatory molecules and increased levels in ASD R(-) proving the involvement of inflammatory changes. The results of this study provide new evidence for specific bioenergetic profiles of immune cells and elevated inflammation-related molecules in ASD. For the first time, data on a unique metabolic profile in ASD R(+) and its comparison with a random group of children of similar age and sex are provided. Our data show that mitochondrial dysfunction is more significant in ASD R(+), while in ASD R(-) inflammation is more pronounced. Probably, in the group without regression, immune mechanisms (immune dysregulation, leading to inflammation) begin initially, and at a later stage mitochondrial activity is also affected under exogenous factors. On the other hand, in the regressed group, the initial damage is in the mitochondria, and perhaps at a later stage immune dysfunction is involved.
Determinants of Interpatient Variability in Treosulfan Pharmacokinetics in AML Patients Undergoing Autologous Stem Cell Transplantation
Authors: Ayçiçek Selin G. , Akhoundova Dilara , Bacher Ulrike , Hayoz Michael , Aebi Yolanda , Largiadèr Carlo R. , Pabst Thomas
Published: July 2024

Limited data on treosulfan pharmacokinetics in adults, particularly regarding autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML), is available to date. Furthermore, correlations between treosulfan exposure, toxicity, and clinical outcome remain understudied. In this single-center retrospective study, we analyzed data from 55 AML patients who underwent HDCT with treosulfan (14 g/m2) and melphalan (140 mg/m2 or 200 mg/m2) (TreoMel) between August 2019 and November 2023 at the University Hospital of Bern. We assessed treosulfan pharmacokinetics and correlations with several physiological parameters with potential impact on its interpatient variability. We further analyzed how treosulfan exposure correlates with toxicity and clinical outcomes. Women above 55 years showed higher area under the curve (AUC) levels (median: 946 mg*h/L, range: 776–1370 mg*h/L), as compared to women under 55 (median: 758 mg*h/L, range: 459–1214 mg*h/L, p = 0.0487). Additionally, women above 55 showed higher peak levels (median: 387 mg/L, range: 308–468 mg/L), as compared to men of the same age range (median: 326 mg/L, range: 264–395 mg/L, p = 0.0159). Treosulfan levels varied significantly with body temperature, liver enzymes, hemoglobin/hematocrit., and treosulfan exposure correlated with diarrhea severity in women over 55 (p = 0.0076). Our study revealed age- and gender-related variability in treosulfan pharmacokinetics, with higher plasma levels observed in female patients above 55. Moreover, our data suggest that treosulfan plasma levels may vary with several physiological parameters and that higher treosulfan exposure may impact toxicity. Our study underlines the need for further research on treosulfan pharmacokinetics, especially in older patients undergoing HDCT in the ASCT setting.
Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer’s Disease
Authors: Sánchez-Puebla Lidia , de Hoz Rosa , Salobrar-García Elena , Arias-Vázquez Alberto , González-Jiménez María , Ramírez Ana I. , Fernández-Albarral José A. , Matamoros José A. , Elvira-Hurtado Lorena , Saido Takaomi C. , Saito Takashi , Nieto Vaquero Carmen , Cuartero María I. , Moro María A. , Salazar Juan J. , López-Cuenca Inés , Ramírez José M.
Published: July 2024

In Alzheimer’s disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans.
The Role of the Gut and Airway Microbiota in Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review
Authors: Gómez-García Manuel , Moreno-Jimenez Emma , Morgado Natalia , García-Sánchez Asunción , Gil-Melcón María , Pérez-Pazos Jacqueline , Estravís Miguel , Isidoro-García María , Dávila Ignacio , Sanz Catalina
Published: July 2024

In recent years, there has been growing interest in understanding the potential role of microbiota dysbiosis or alterations in the composition and function of human microbiota in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). This systematic review evaluated the literature on CRSwNP and host microbiota for the last ten years, including mainly nasal bacteria, viruses, and fungi, following the PRISMA guidelines and using the major scientific publication databases. Seventy original papers, mainly from Asia and Europe, met the inclusion criteria, providing a comprehensive overview of the microbiota composition in CRSwNP patients and its implications for inflammatory processes in nasal polyps. This review also explores the potential impact of microbiota-modulating therapies for the CRSwNP treatment. Despite variability in study populations and methodologies, findings suggest that fluctuations in specific taxa abundance and reduced bacterial diversity can be accepted as critical factors influencing the onset or severity of CRSwNP. These microbiota alterations appear to be implicated in triggering cell-mediated immune responses, cytokine cascade changes, and defects in the epithelial barrier. Although further human studies are required, microbiota-modulating strategies could become integral to future combined CRSwNP treatments, complementing current therapies that mainly target inflammatory mediators and potentially improving patient outcomes.
Genome-Wide Identification and Analysis of SUS and AGPase Family Members in Sweet Potato: Response to Excessive Nitrogen Stress during Storage Root Formation
Authors: Han Shaoxuan , Lin Yanhui , Meng Yayi , Si Chengcheng
Published: July 2024

(1) The development of sweet potato storage roots is impacted by nitrogen (N) levels, with excessive nitrogen often impeding development. Starch synthesis enzymes such as sucrose synthase (SUS) and ADP-glucose pyrophosphorylase (AGPase) are pivotal in this context. Although the effects of excessive nitrogen on the formation of sweet potato storage roots are well documented, the specific responses of IbSUSs and IbAGPases have not been extensively reported on. (2) Pot experiments were conducted using the sweet potato cultivar “Pushu 32” at moderate (MN, 120 kg N ha−1) and excessive nitrogen levels (EN, 240 kg N ha−1). (3) Nine IbSUS and nine IbAGPase genes were categorized into three and two distinct subgroups based on phylogenetic analysis. Excessive nitrogen significantly (p < 0.05) suppressed the expression of IbAGPL1, IbAGPL2, IbAGPL4, IbAGPL5, IbAGPL6, IbAGPS1, and IbAGPS2 in fibrous roots and IbSUS2, IbSUS6, IbSUS7, IbSUS8, IbSUS9, IbAGPL2, and IbAGPL4 in storage roots, and then significantly (p < 0.05) decreased the SUS and AGPase activities and starch content of fibrous root and storage root, ultimately reducing the storage root formation of sweet potato. Excessive nitrogen extremely significantly (p < 0.01) enhanced the expression of IbAGPL3, which was strongly negatively correlated with the number and weight of storage roots per plant. (4) IbAGPL3 may be a key gene in the response to excessive nitrogen stress and modifying starch synthesis in sweet potato.
Skin Aging and the Upcoming Role of Ferroptosis in Geroscience
Authors: Rezzani Rita , Favero Gaia , Cominelli Giorgia , Pinto Daniela , Rinaldi Fabio
Published: July 2024

The skin is considered the most important organ system in mammals, and as the population ages, it is important to consider skin aging and anti-aging therapeutic strategies. Exposure of the skin to various insults induces significant changes throughout our lives, differentiating the skin of a young adult from that of an older adult. These changes are caused by a combination of intrinsic and extrinsic aging. We report the interactions between skin aging and its metabolism, showing that the network is due to several factors. For example, iron is an important nutrient for humans, but its level increases with aging, inducing deleterious effects on cellular functions. Recently, it was discovered that ferroptosis, or iron-dependent cell death, is linked to aging and skin diseases. The pursuit of new molecular targets for ferroptosis has recently attracted attention. Prevention of ferroptosis is an effective therapeutic strategy for the treatment of diseases, especially in old age. However, the pathological and biological mechanisms underlying ferroptosis are still not fully understood, especially in skin diseases such as melanoma and autoimmune diseases. Only a few basic studies on regulated cell death exist, and the challenge is to turn the studies into clinical applications.
Nuclear Factor-Kappa-B Mediates the Advanced Glycation End Product-Induced Repression of Slc2a4 Gene Expression in 3T3-L1 Adipocytes
Authors: Michalani Maria Luiza Estimo , Passarelli Marisa , Machado Ubiratan Fabres
Published: July 2024

Advanced glycated end products (AGEs) are cytotoxic compounds that are mainly increased in diabetes mellitus (DM), kidney failure, inflammation, and in response to the ingestion of AGE-rich diets. AGEs can also impair glycemic homeostasis by decreasing the expression of the Slc2a4 (solute carrier family 2 member 4) gene and its GLUT4 (solute carrier family 2, facilitated glucose transporter member 4) protein in muscle. However, the mechanisms underlying AGE’s effect on adipocytes have not been demonstrated yet. This study investigated the effects of AGEs upon Slc2a4/GLUT4 expression in 3T3-L1 adipocytes, as well as the potential role of NFKB (nuclear factor NF-kappa-B) activity in the effects observed. Adipocytes were cultured in the presence of control albumin (CA) or advanced glycated albumin (GA) at concentrations of 0.4, 3.6, and 5.4 mg/mL for 24 h or 72 h. Slc2a4, Rela, and Nfkb1mRNAs were measured by RT-qPCR, GLUT4, IKKA/B, and p50/p65 NFKB subunits using Western blotting, and p50/p65 binding into the Slc2a4 promoter was analyzed by chromatin immunoprecipitation (ChIP) assay. GA at 0.4 mg/mL increased Slc2a4/GLUT4 expression after 24 h and 72 h (from 50% to 100%), but at 5.4 mg/mL, Slc2a4/GLUT4 expression decreased at 72 h (by 50%). Rela and Nfkb1 expression increased after 24 h at all concentrations, but this effect was not observed at 72 h. Furthermore, 5.4 mg/mL of GA increased the p50/p65 nuclear content and binding into Slc2a4 at 72 h. In summary, this study reveals AGE-induced and NFKB-mediated repression of Slc2a4/GLUT4 expression. This can compromise the adipocyte glucose utilization, contributing not only to the worsening of glycemic control in DM subjects but also the impairment of glycemic homeostasis in non-DM subjects under the high intake of AGE-rich foods.
Identification and Characterization of miRNAs and lncRNAs Associated with Salinity Stress in Rice Panicles
Authors: Jiang Conghui , Wang Yulong , He Yanan , Peng Yongbin , Xie Lixia , Li Yaping , Sun Wei , Zhou Jinjun , Zheng Chongke , Xie Xianzhi
Published: July 2024

Salinity is a common abiotic stress that limits crop productivity. Although there is a wealth of evidence suggesting that miRNA and lncRNA play important roles in the response to salinity in rice seedlings and reproductive stages, the mechanism by which competing endogenous RNAs (ceRNAs) influence salt tolerance and yield in rice has been rarely reported. In this study, we conducted full whole-transcriptome sequencing of rice panicles during the reproductive period to clarify the role of ceRNAs in the salt stress response and yield. A total of 214 lncRNAs, 79 miRNAs, and 584 mRNAs were identified as differentially expressed RNAs under salt stress. Functional analysis indicates that they play important roles in GO terms such as response to stress, biosynthesis processes, abiotic stimuli, endogenous stimulus, and response to stimulus, as well as in KEGG pathways such as secondary metabolite biosynthesis, carotenoid biosynthesis, metabolic pathways, and phenylpropanoid biosynthesis. A ceRNA network comprising 95 lncRNA–miRNA–mRNA triplets was constructed. Two lncRNAs, MSTRG.51634.2 and MSTRG.48576.1, were predicted to bind to osa-miR172d-5p to regulate the expression of OsMYB2 and OsMADS63, which have been reported to affect salt tolerance and yield, respectively. Three lncRNAs, MSTRG.30876.1, MSTRG.44567.1, and MSTRG.49308.1, may bind to osa-miR5487 to further regulate the expression of a stress protein (LOC_Os07g48460) and an aquaporin protein (LOC_Os02g51110) to regulate the salt stress response. This study is helpful for understanding the underlying molecular mechanisms of ceRNA that drive the response of rice to salt stress and provide new genetic resources for salt-resistant rice breeding.
Transcriptomic and Metabolomic Analyses Reveal Molecular Regulatory Networks for Pigmentation Deposition in Sheep
Authors: Zhang Mancheng , Xu Xiaoli , Chen Yuan , Wei Chengqi , Zhan Siyuan , Cao Jiaxue , Guo Jiazhong , Dai Dinghui , Wang Linjie , Zhong Tao , Zhang Hongping , Li Li
Published: July 2024

Domestic animals have multiple phenotypes of skin and coat color, which arise from different genes and their products, such as proteins and metabolites responsible with melanin deposition. However, the complex regulatory network of melanin synthesis remains to be fully unraveled. Here, the skin and tongue tissues of Liangshan black sheep (black group) and Liangshan semi-fine-wool sheep (pink group) were collected, stained with hematoxylin–eosin (HE) and Masson–Fontana, and the transcriptomic and metabolomic data were further analyzed. We found a large deposit of melanin granules in the epidermis of the black skin and tongue. Transcriptome and metabolome analysis identified 744 differentially expressed genes (DEGs) and 443 differentially expressed metabolites (DEMs) between the pink and black groups. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed the DEGs and DEMs were mainly enriched in the pathways of secondary metabolic processes, melanin biosynthesis processes, melanin metabolism processes, melanosome membranes, pigment granule membranes, melanosome, tyrosine metabolism, and melanogenesis. Notably, we revealed the gene ENSARG00020006042 may be a family member of YWHAs and involved in regulating melanin deposition. Furthermore, several essential genes (TYR, TYRP1, DCT, PMEL, MLANA, SLC45A2) were significantly associated with metabolite prostaglandins and compounds involved in sheep pigmentation. These findings provide new evidence of the strong correlation between prostaglandins and related compounds and key genes that regulate sheep melanin synthesis, furthering our understanding of the regulatory mechanisms and molecular breeding of pigmentation in sheep.
Early and Late Effects of Low-Dose X-ray Exposure in Human Fibroblasts: DNA Repair Foci, Proliferation, Autophagy, and Senescence
Authors: Osipov Andrey , Chigasova Anna , Yashkina Elizaveta , Ignatov Maxim , Vorobyeva Natalia , Zyuzikov Nikolay , Osipov Andreyan N.
Published: July 2024

The effects of low-dose radiation exposure remain a controversial topic in radiation biology. This study compares early (0.5, 4, 24, 48, and 72 h) and late (5, 10, and 15 cell passages) post-irradiation changes in γH2AX, 53BP1, pATM, and p-p53 (Ser-15) foci, proliferation, autophagy, and senescence in primary fibroblasts exposed to 100 and 2000 mGy X-ray radiation. The results show that exposure to 100 mGy significantly increased γH2AX, 53BP1, and pATM foci only at 0.5 and 4 h post irradiation. There were no changes in p-p53 (Ser-15) foci, proliferation, autophagy, or senescence up to 15 passages post irradiation at the low dose.
Inflammation, Oxidative Stress, and Endothelial Dysfunction in the Pathogenesis of Vascular Damage: Unraveling Novel Cardiovascular Risk Factors in Fabry Disease
Authors: Faro Denise Cristiana , Di Pino Francesco Lorenzo , Monte Ines Paola
Published: July 2024

Anderson-Fabry disease (AFD), a genetic disorder caused by mutations in the α-galactosidase-A (GLA) gene, disrupts lysosomal function, leading to vascular complications. The accumulation of globotriaosylceramide (Gb3) in arterial walls triggers upregulation of adhesion molecules, decreases endothelial nitric oxide synthesis, and induces reactive oxygen species production. This cascade results in fibrotic thickening, endothelial dysfunction, hypercontractility, vasospasm, and a pro-thrombotic phenotype. AFD patients display increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating heightened cardiovascular risk. Nailfold capillaroscopy (NFC) shows promise in diagnosing and monitoring microcirculatory disorders in AFD, though it remains underexplored. Morphological evidence of AFD as a storage disorder can be demonstrated through electron microscopy and immunodetection of Gb3. Secondary pathophysiological disturbances at cellular, tissue, and organ levels contribute to the clinical manifestations, with prominent lysosomal inclusions observed in vascular, cardiac, renal, and neuronal cells. Chronic accumulation of Gb3 represents a state of ongoing toxicity, leading to increased cell turnover, particularly in vascular endothelial cells. AFD-related vascular pathology includes increased renin-angiotensin system activation, endothelial dysfunction, and smooth muscle cell proliferation, resulting in IMT increase. Furthermore, microvascular alterations, such as atypical capillaries observed through NFC, suggest early microvascular involvement. This review aims to unravel the complex interplay between inflammation, oxidative stress, and endothelial dysfunction in AFD, highlighting the potential connections between metabolic disturbances, oxidative stress, inflammation, and fibrosis in vascular and cardiac complications. By exploring novel cardiovascular risk factors and potential diagnostic tools, we can advance our understanding of these mechanisms, which extend beyond sphingolipid accumulation to include other significant contributors to disease pathogenesis. This comprehensive approach can pave the way for innovative therapeutic strategies and improved patient outcomes.
Green Extraction of Reed Lignin: The Effect of the Deep Eutectic Solvent Composition on the UV-Shielding and Antioxidant Properties of Lignin
Authors: Morozova Olga , Vasil’eva Irina , Shumakovich Galina , Khlupova Maria , Chertkov Vyacheslav , Shestakova Alla , Yaropolov Alexander
Published: July 2024

Lignin, the second most abundant natural polymer, is a by-product of the biorefinery and pulp and paper industries. This study was undertaken to evaluate the properties and estimate the prospects of using lignin as a by-product of the pretreatment of common reed straw (Phragmites australis) with deep eutectic solvents (DESs) of various compositions: choline chloride/oxalic acid (ChCl/OA), choline chloride/lactic acid (ChCl/LA), and choline chloride/monoethanol amine (ChCl/EA). The lignin samples, hereinafter referred to as Lig-OA, Lig-LA, and Lig-EA, were obtained as by-products after optimizing the conditions of reed straw pretreatment with DESs in order to improve the efficiency of subsequent enzymatic hydrolysis. The lignin was studied using gel penetration chromatography, UV-vis, ATR-FTIR, and 1H and 13C NMR spectroscopy; its antioxidant activity was assessed, and the UV-shielding properties of lignin/polyvinyl alcohol composite films were estimated. The DES composition had a significant impact on the structure and properties of the extracted lignin. The lignin’s ability to scavenge ABTS+• and DPPH• radicals, as well as the efficiency of UV radiation shielding, decreased as follows: Lig-OA > Lig-LA > Lig-EA. The PVA/Lig-OA and PVA/Lig-LA films with a lignin content of 4% of the weight of PVA block UV radiation in the UVA range by 96% and 87%, respectively, and completely block UV radiation in the UVB range.
Peripheral Blood Mononuclear Cells and Serum Cytokines in Patients with Lupus Nephritis after COVID-19
Authors: Lisowska Katarzyna A. , Ciesielska-Figlon Klaudia , Komorniczak Michał , Bułło-Piontecka Barbara , Dębska-Ślizień Alicja , Wardowska Anna
Published: July 2024

Systemic lupus erythematosus (SLE) patients have an increased risk of infections and infection-related mortality. Therefore, during the global SARS-CoV-2 pandemic, SLE patients were particularly vulnerable to SARS-CoV-2 infections. Also, compared to other patients, SLE patients seem to develop more severe manifestations of coronavirus disease 2019 (COVID-19), with higher rates of hospitalization, invasive ventilation requirements, or death. This study evaluated the immune parameters after SARS-CoV-2 infection in SLE patients. We analyzed subpopulations of peripheral blood cells collected from patients with renal manifestation of SLE (lupus nephritis, LN). LN patients were divided into two subgroups: those unexposed to SARS-CoV-2 (LN CoV-2(−)) and those who had confirmed COVID-19 (LN-CoV-2(+)) six months earlier. We analyzed basic subpopulations of T cells, B cells, monocytes, dendritic cells (DCs), and serum cytokines using flow cytometry. All collected data were compared to a healthy control group without SARS-CoV-2 infection in medical history. LN patients were characterized by a decreased percentage of helper T (Th) cells and an increased percentage of cytotoxic T (Tc) cells regardless of SARS-CoV-2 infection. LN CoV-2(+) patients had a higher percentage of regulatory T cells (Tregs) and plasmablasts (PBs) and a lower percentage of non-switched memory (NSM) B cells compared to LN CoV-2(−) patients or healthy controls (HC CoV-2(−)). LN patients had a higher percentage of total monocytes compared with HC CoV-2(−). LN CoV-2(+) patients had a higher percentage of classical and intermediate monocytes than LN CoV-2(−) patients and HC CoV-2(−). LN CoV-2(+) patients had higher serum IL-6 levels than HC CoV-2(−), while LN CoV-2(−) patients had higher levels of serum IL-10. LN patients are characterized by disturbances in the blood’s basic immunological parameters. However, SARS-CoV-2 infection influences B-cell and monocyte compartments.
Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments
Authors: Yue Jianda , Yin Yekui , Feng Xujun , Xu Jiawei , Li Yaqi , Li Tingting , Liang Songping , He Xiao , Liu Zhonghua , Wang Ying
Published: July 2024

In the development and progression of cervical cancer, oxidative stress plays an important role within the cells. Among them, Solute Carrier Family 7 Member 11 (SLC7A11/xCT) is crucial for maintaining the synthesis of glutathione and the antioxidant system in cervical cancer cells. In various tumor cells, studies have shown that SLC7A11 inhibits ferroptosis, a form of cell death, by mediating cystine uptake and maintaining glutathione synthesis. Additionally, SLC7A11 is also involved in promoting tumor metastasis and immune evasion. Therefore, inhibiting the SLC7A11/xCT axis has become a potential therapeutic strategy for cervical cancer. In this study, through structure-based high-throughput virtual screening, a compound targeting the SLC7A11/xCT axis named compound 1 (PubChem CID: 3492258) was discovered. In vitro experiments using HeLa cervical cancer cells as the experimental cell model showed that compound 1 could reduce intracellular glutathione levels, increase glutamate and reactive oxygen species (ROS) levels, disrupt the oxidative balance within HeLa cells, and induce cell death. Furthermore, molecular dynamics simulation results showed that compound 1 has a stronger binding affinity with SLC7A11 compared to the positive control erastin. Overall, all the results mentioned above indicate the potential of compound 1 in targeting the SLC7A11/xCT axis and treating cervical cancer both in vitro and in silico.
Lipoprotein Lipidomics as a Frontier in Non-Alcoholic Fatty Liver Disease Biomarker Discovery
Authors: Herrera-Marcos Luis V. , Arbones-Mainar Jose M. , Osada Jesús
Published: July 2024

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics. This technology, based on the combination of chromatography and mass spectrometry, has been extensively used to explore the lipid metabolism of NAFLD. In this review, we aim to summarize the knowledge gained through lipidomics assays exploring tissues, plasma, and lipoproteins from individuals with NAFLD. Our goal is to identify common features and active pathways that could facilitate the finding of a reliable biomarker from this field. The most frequent observation was a variable decrease (1–9%) in polyunsaturated fatty acids in phospholipids and non-esterified fatty acids in NAFLD patients, both in plasma and liver. Additionally, a reduction in phosphatidylcholines is a common feature in the liver. Due to the scarcity of studies, further research is needed to properly detect lipoprotein, plasma, and tissue lipid signatures of NAFLD etiologies, and NAFLD subtypes, and to define the relevance of this technology in disease management strategies in the push toward personalized medicine.
Antidepressant-like and Beneficial Effects of a Neoponcirin-Beta-Cyclodextrin Inclusion Complex in Mice Exposed to Prolonged Stress
Authors: López Méndez Luis José , Martínez-Mota Lucía , Cassani Julia , Mayagoitia-Novales Lilian , Benítez-King Gloria , Becerril-Villanueva Luis Enrique , Dorantes-Barrón Ana María , Jurado-Hernández Noé , Estrada-Reyes Rosa
Published: July 2024

Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/βCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/βCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/βCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice’s expression of stress-related inflammatory cytokines (IL-1β, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/βCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/βCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1β levels. The effects of the NEO/βCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress.
Decoding the Chloroplast Genome of Tetrastigma (Vitaceae): Variations and Phylogenetic Selection Insights
Authors: Zhu Junqiao , Huang Yang , Chai Weiguo , Xia Pengguo
Published: July 2024

Tetrastigma (Vitaceae) is known for its ornamental, medicinal, and ecological significance. However, the structural and variational characteristics of the Tetrastigma chloroplast genome and their impact on phylogenetic relationships remain underexplored. This study utilized bioinformatics methods to assemble and annotate the chloroplast genomes of 10 Tetrastigma species and compare them with five previously sequenced species. This study analyzed gene composition, simple sequence repeats, and codon usage patterns, revealing a high A/T content, uniquely identified pentanucleotide repeats in five species and several preferred codons. In addition, comparative analyses were conducted of the chloroplast genomes of 15 Tetrastigma species, examining their structural differences and identifying polymorphic hotspots (rps16, rps16-trnQ, trnS, trnD, psbC-trnS-psbZ, accD-psaI, psbE-petL-petG, etc.) suitable for DNA marker development. Furthermore, phylogenetic and selective pressure analyses were performed based on the chloroplast genomes of these 15 Tetrastigma species, validating and elucidating intra-genus relationships within Tetrastigma. Futhermore, several genes under positive selection, such as atpF and accD, were identified, shedding light on the adaptive evolution of Tetrastigma. Utilizing 40 Vitaceae species, the divergence time of Tetrastigma was estimated, clarifying the evolutionary relationships within Tetrastigma relative to other genera. The analysis revealed diverse divergences of Tetrastigma in the Miocene and Pliocene, with possible ancient divergence events before the Eocene. Furthermore, family-level selective pressure analysis identified key features distinguishing Tetrastigma from other genera, showing a higher degree of purifying selection. This research enriches the chloroplast genome data for Tetrastigma and offers new insights into species identification, phylogenetic analysis, and adaptive evolution, enhancing our understanding of the genetic diversity and evolutionary history of these species.
Persistence of Infectious Canine Distemper Virus in Murine Xenotransplants of Canine Histiocytic Sarcoma Cells after Intratumoral Application
Authors: Lombardo Mara Sophie , Armando Federico , Marek Katarzyna , Rohn Karl , Baumgärtner Wolfgang , Puff Christina
Published: July 2024

Oncolytic viruses and morbilliviruses in particular, represent an interesting therapeutic approach for tumors with a poor prognosis and frequent resistance to conventional therapies. Canine histiocytic sarcomas (HS) exemplify such a neoplasm in need for new curative approaches. Previous investigations demonstrated a limited success of an acute intratumoral application of canine distemper virus (CDV) on xenotransplanted canine histiocytic sarcoma cells (DH82 cells), while persistently CDV-infected DH82 cell transplants exhibited a complete spontaneous regression. Therefore, the present study focuses on an intratumoral application of persistently CDV vaccine strain Onderstepoort-infected DH82 (DH82 Ond p.i.) cells into non-infected subcutaneous DH82 cell transplants in a murine model. DH82 cell transplants that received 10 applications, two days apart, showed a transient growth retardation as well as larger areas of intratumoral necrosis, lower mitotic rates, and a decreased intratumoral vascularization compared to controls. Viral mRNA was detected in all neoplasms following application of DH82 Ond p.i. cells until 66 days after the last injection. Furthermore, infectious virus was present until 62 days after the last injection. Although complete regression was not achieved, the present application regimen provides promising results as a basis for further treatments, particularly with genetically modified viruses, to enhance the observed effects.
The Association of Genetic Markers Involved in Muscle Performance Responding to Lactate Levels during Physical Exercise Therapy by Nordic Walking in Patients with Long COVID Syndrome: A Nonrandomized Controlled Pilot Study
Authors: Lizcano-Álvarez Ángel , Varillas-Delgado David , Cano-de-la-Cuerda Roberto , Jiménez-Antona Carmen , Melián-Ortiz Alberto , Molero-Sánchez Alberto , Laguarta-Val Sofía
Published: July 2024

Several genetic markers have shown associations with muscle performance and physical abilities, but the response to exercise therapy is still unknown. The aim of this study was to test the response of patients with long COVID through an aerobic physical therapy strategy by the Nordic walking program and how several genetic polymorphisms involved in muscle performance influence physical capabilities. Using a nonrandomized controlled pilot study, 29 patients who previously suffered from COVID-19 (long COVID = 13, COVID-19 = 16) performed a Nordic walking exercise therapy program for 12 sessions. The influence of the ACE (rs4646994), ACTN3 (rs1815739), AMPD1 (rs17602729), CKM (rs8111989), and MLCK (rs2849757 and rs2700352) polymorphisms, genotyped by using single nucleotide primer extension (SNPE) in lactic acid concentration was established with a three-way ANOVA (group × genotype × sessions). For ACE polymorphism, the main effect was lactic acid (p = 0.019). In ACTN3 polymorphism, there were no main effects of lactic acid, group, or genotype. However, the posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CT and TT genotypes (all p < 0.05). For AMPD1 polymorphism, there were main effects of lactic acid, group, or genotype and lactic acid × genotype or lactic acid × group × genotype interactions (all p < 0.05). The posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CC and CT genotypes (all p < 0.05). Physical therapy strategy through Nordic walking enhanced physical capabilities during aerobic exercise in post-COVID19 patients with different genotypes in ACTN3 c.1729C>T and AMPD1 c.34C>T polymorphisms. These findings suggest that individuals who reported long COVID who presumably exercised less beforehand appeared to be less able to exercise, based on lactate levels, and the effect of aerobic physical exercise enhanced physical capabilities conditioned by several genetic markers in long COVID patients.
Calcium-Dependent Protein Kinase GhCDPK16 Exerts a Positive Regulatory Role in Enhancing Drought Tolerance in Cotton
Authors: Yan Mengyuan , Chai Meijie , Li Libei , Dong Zhiwei , Jin Hongmiao , Tan Ming , Ye Ziwei , Yu Shuxun , Feng Zhen
Published: July 2024

Cotton is essential for the textile industry as a primary source of natural fibers. However, environmental factors like drought present significant challenges to its cultivation, adversely affecting both production levels and fiber quality. Enhancing cotton’s drought resilience has the potential to reduce yield losses and support the growth of cotton farming. In this study, the cotton calcium-dependent protein kinase GhCDPK16 was characterized, and the transcription level of GhCDPK16 was significantly upregulated under drought and various stress-related hormone treatments. Physiological analyses revealed that the overexpression of GhCDPK16 improved drought stress resistance in Arabidopsis by enhancing osmotic adjustment capacity and boosting antioxidant enzyme activities. In contrast, silencing GhCDPK16 in cotton resulted in increased dehydration compared with the control. Furthermore, reduced antioxidant enzyme activities and downregulation of ABA-related genes were observed in GhCDPK16-silenced plants. These findings not only enhanced our understanding of the biological functions of GhCDPK16 and the mechanisms underlying drought stress resistance but also underscored the considerable potential of GhCDPK16 in improving drought resilience in cotton.