bluuebunny/crossref_metadata_2025 huggingface dataset:
Aloe vera Cuticle: A Promising Organic Water-Retaining Agent for Agricultural Use
Authors: Luligo-Montealegre Wilmer E. , Prado-Alzate Santiago , Ayala-Aponte Alfredo , Tirado Diego F. , Serna-Cock Liliana
Published: July 2024

Water is an important resource for both human and environmental survival. However, due to current human practices, we are facing a serious crisis in accessing water. Thus, solutions must be explored to optimize the use of this resource. In the search for an organic water-retaining agent for agricultural use, the techno-functional properties of Aloe vera (Aloe barbadensis Miller) cuticle, an agro-industrial residue generated after gel extraction, were evaluated. The residue was dried and ground. The effects of particle size (180 µm and 250 µm), temperature (10 °C, 20 °C, 30 °C, and 40 °C), and pH (4.5, 6.0, and 7.0) on the solubility and water-holding capacity (WHC) of the obtained product (i.e., hydrogel) were then evaluated. The treatment with the highest WHC was selected and compared with the WHC of a commercial synthetic polyacrylamide gel widely used in agriculture. The effects of KNO3 and Ca(NO3)2 at different concentrations (10 g L−1, 20 g L−1, 30 g L−1, and 40 g L−1) on the WHC of the gels were assessed. Particle size, temperature, and pH interactions had statistically significant effects on solubility, while the WHC was affected by particle size × temperature and pH × temperature interactions. The highest product solubility (75%) was obtained at the smallest particle size (i.e., 180 µm), pH 4.5, and 20 °C. Meanwhile, the highest WHC (18 g g−1) was obtained at the largest particle size (i.e., 250 µm), pH 6.0, and 20 °C. This optimized gel kept its WHC across both salts and their concentrations. In contrast, the commercial gel significantly decreased its WHC with salt concentration. The product elaborated with A. vera cuticle could have bioeconomic potential as a water-retention agent for agricultural use, with the advantage that it is not affected by the addition of salts used for plant fertilization.
The Role of BrKS in Leafy Head Formation Was Confirmed by Two Allelic Mutants of Chinese Cabbage (Brassica rapa L. ssp. pekinensis)
Authors: Qu Gaoyang , Liu Shihang , Wang Wei , Wei Shixiang , Liu Yuanwei , Gao Yue , Feng Hui
Published: July 2024

Considering that the presence of a leafy head is a key morphological characteristic that determines the yield and quality of Chinese cabbage, identifying the major genes regulating the formation of a leafy head is crucial for variety improvement. A heading-related gene, BrKS, was previously predicted from a non-heading mutant, nhm1, derived from a heading variety, which encodes a key enzyme involved in gibberellin biosynthesis. Here, another mutant, nhm2, was identified from the same EMS-mutagenized population, and the phenotype of nhm2 was consistent with that of nhm1. We crossed mutants nhm1 and nhm2, and their F1 plants exhibited the mutant phenotype, which indicated that their mutant genes were allelic. A single non-synonymous mutation in the fourth exon of BrKS in mutant nhm1 and another single non-synonymous mutation in the tenth exon of BrKS in mutant nhm2. The same gene mutation in mutants nhm1 and nhm2 produced a similar non-heading phenotype, which confirmed the role of BrKS in the leafy head formation of Chinese cabbage. RNA-Seq analysis indicated that a transcription factor gene, BrERF1A, which is associated with leaf development, significantly down-regulated expression in mutant nhm1, and after the mutant was treated with GA3, the expression level of BrERF1A was recovered, which indicated that BrKS might be involved in leafy head formation through regulating the expression level of BrERF1A. Our findings provide important clues for revealing the molecular mechanism of leafy head formation in Chinese cabbage.
A Review on Biocontrol Agents as Sustainable Approach for Crop Disease Management: Applications, Production, and Future Perspectives
Authors: Tyagi Anshika , Lama Tamang Tensangmu , Kashtoh Hamdy , Mir Rakeeb Ahmad , Mir Zahoor Ahmad , Manzoor Subaya , Manzar Nazia , Gani Gousia , Vishwakarma Shailesh Kumar , Almalki Mohammed A. , Ali Sajad
Published: July 2024

Horticultural crops are vulnerable to diverse microbial infections, which have a detrimental impact on their growth, fruit quality, and productivity. Currently, chemical pesticides are widely employed to manage diseases in horticultural crops, but they have negative effects on the environment, human health, soil physiochemical properties, and biodiversity. Additionally, the use of pesticides has facilitated the development and spread of resistant pathovars, which have emerged as a serious concern in contemporary agriculture. Nonetheless, the adverse consequences of chemical pesticides on the environment and public health have worried scientists greatly in recent years, which has led to a switch to the use of biocontrol agents such as bacteria, fungi, and insects to control plant pathogens. Biocontrol agents (BCAs) form an integral part of organic farming, which is regarded as the future of sustainable agriculture. Hence, harnessing the potential of BCAs is an important viable strategy to control microbial disease in horticultural crops in a way that is also ecofriendly and can improve the soil health. Here, we discuss the role of the biological control of microbial diseases in crops. We also discuss different microbial-based BCAs such as fungal, bacterial, and viral and their role in disease management. Next, we discuss the factors that affect the performance of the BCAs under field conditions. This review also highlights the genetic engineering of BCAs to enhance their biocontrol efficiency and other growth traits. Finally, we highlight the challenges and opportunities of biocontrol-based disease management in horticulture crops and future research directions to boost their efficacy and applications.
Burnout and Attention Failure in STEM: The Role of Self-Control and the Buffer of Mindfulness
Authors: Saxena Mahima
Published: July 2024

Drawing on self-regulatory strength models of self-control, this research examined the relationship between burnout and attentional processes for STEM (science, technology, engineering, and mathematics) students. Using data from participants in STEM, burnout was found to be associated with higher levels of off-task thinking, also known as mind-wandering. Further, self-control acted as a mediator in the relationship between burnout and mind-wandering such that higher levels of burnout predicted poor self-control that subsequently increased the mind’s tendency to wander. Additionally, mindfulness buffered the relationship between burnout and mind-wandering such that burnout had the most detrimental impact on attention for those students who were low in mindfulness. Using the Johnson-Neyman approach, results reveal the upper limits for the moderating impact of mindfulness. Results and implications for science and practice are discussed with a special grounding for students in the STEM context.
Breast Cancer Screening among African Immigrants in the United States: An Integrative Review of Barriers, Facilitators, and Interventions
Authors: Rauch Julian I. , Daniels Joseph , Robillard Alyssa , Joseph Rodney P.
Published: July 2024

The purpose of this review was to synthesize the available literature on breast cancer-screening barriers, facilitators, and interventions among U.S. African immigrants. Following the integrative review framework and PRISMA guidelines for reporting systemic reviews, five electronic databases were searched: PubMed, CINAHL, PsycINFO, Medline, and Google Scholar. Studies were included if they were published in English language journals after 1 January 2000 and reported data on breast cancer-screening barriers, facilitators, or interventions among U.S. African immigrants. Barriers and facilitators reported by studies were descriptively examined and synthesized by two authors and classified as aligning with one of the three levels of influences based on the social–ecological model (intrapersonal, interpersonal, and community). Interventions promoting breast cancer screening were narratively summarized. Search procedures retrieved 1011 articles, with 12 meeting the criteria for inclusion in the review (6 qualitative and 6 quantitative). Intrapersonal barriers included limited awareness, fear of pain, language barriers, health concerns, transportation issues, costs, and negative past experiences. Interpersonal barriers involved modesty, spiritual beliefs, and lack of support, while community-level barriers included provider and healthcare-system challenges. Regarding facilitators, past screening experiences and health insurance were the most commonly reported intrapersonal facilitators. The only interpersonal facilitator identified was observing other women experience a breast cancer diagnosis and undergo treatment. Community-level facilitators included appointment reminders, scheduling assistance, culturally congruent interpreters, transportation to screening facilities, and patient navigators. Three articles reported outcomes of breast cancer-screening interventions. All three were pilot studies and reported increased knowledge and attitudes regarding breast cancer screening following the respective interventions. One study examined the uptake of breast cancer screening following the intervention, with results indicating an increase in screening. Findings provide a comprehensive synthesis of factors influencing breast cancer screening among African immigrants and highlight the need for future research on the topic. This review was registered with Prospero (CRD42024502826) before the initiation of search procedures.
Comprehensive Criteria for Reporting Qualitative Research (CCQR): Reporting Guideline for Global Health Qualitative Research Methods
Authors: Sinha Priyanka , Paudel Binita , Mosimann Tamara , Ahmed Hanan , Kovane Gaotswake Patience , Moagi Miriam , Phuti Angel
Published: July 2024

Globally, the demand for qualitative research has risen, driven by the health sector’s need for in-depth investigation of complex issues behind any phenomenon that may be inadequately comprehended and that other research methods cannot explore, uncover, or describe. The authors aimed to improve the accessibility and comprehensiveness of reporting guidelines for qualitative research. A comprehensive review of scientific articles was conducted on PubMed, Medline, CINAHL, and Embase, and it retrieved 1989 articles plus 13 more articles through the snowball method. After screening, 17 key articles were identified, which led to the development of Comprehensive Criteria for Reporting Qualitative Research that comprises 14 categories, offering key elements in an organized table. This novel guideline complements the two widely used guidelines, Consolidated Criteria for Reporting Qualitative Research and Standards for Reporting Qualitative Research, by including additional aspects like objectives, existing knowledge, rationale behind methodologies, conclusions, recommendations, and reference citations. The study responds to the rising need for improved qualitative research reporting guidelines in global health.
Analyzing Overnight Momentum Transmission: The Impact of Oil Price Volatility on Global Financial Markets
Authors: Alqaralleh Huthaifa Sameeh
Published: July 2024

Fluctuations in oil prices substantially impact both the real economy and international financial markets. Despite extensive studies on oil market dynamics and overnight momentum, a comprehensive understanding of the link between oil price changes and energy market momentum, as well as their broader influence on global financial markets, remains elusive. This study delves into the intricate mechanics of overnight momentum transmission within financial markets, focusing on its origin in oil price fluctuations and its overarching impact on market dynamics. Employing the quantile VAR method, we analyze daily market data from 3 January 2014 to 17 January 2024. This study emphasizes the significance of overnight momentum on the transmission of volatility, particularly in the tails of the distribution, and highlights the necessity for efficient strategies to govern financial stability. The shale oil revolution, COVID-19, the Russia–Ukraine war, and the Israel–Hamas conflict have significantly impacted the interconnectivity of financial markets on a global scale. It is crucial for policymakers to give priority to the monitoring of the energy market to reduce risks and improve the resilience of the system.
Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis
Authors: Han Jung Woo , Chang Hun Soo , Park Sung Chul , Yang Jin Young , Kim Ye Ji , Kim Jin Ha , Park Hyo Song , Jeong Han , Lee Junwon , Yoon Chang Ki , Yu Hyung Gon , Woo Se Joon , Lyu Jungmook , Park Tae Kwann
Published: July 2024

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.
A Novel Luciferase-Based Reporter Gene Technology for Simultaneous Optical and Radionuclide Imaging of Cells
Authors: Gaspar Natasa , Handula Maryana , Stroet Marcus C. M. , Marella-Panth Kranthi , Haeck Joost , Kirkland Thomas A. , Hall Mary P. , Encell Lance P. , Dalm Simone , Lowik Clemens , Seimbille Yann , Mezzanotte Laura
Published: July 2024

Multimodality reporter gene imaging combines the sensitivity, resolution and translational potential of two or more signals. The approach has not been widely adopted by the animal imaging community, mainly because its utility in this area is unproven. We developed a new complementation-based reporter gene system where the large component of split NanoLuc luciferase (LgBiT) presented on the surface of cells (TM-LgBiT) interacts with a radiotracer consisting of the high-affinity complementary HiBiT peptide labeled with a radionuclide. Radiotracer uptake could be imaged in mice using SPECT/CT and bioluminescence within two hours of implanting reporter-gene-expressing cells. Imaging data were validated by ex vivo biodistribution studies. Following the demonstration of complementation between the TM-LgBiT protein and HiBiT radiotracer, we validated the use of the technology in the highly specific in vivo multimodal imaging of cells. These findings highlight the potential of this new approach to facilitate the advancement of cell and gene therapies from bench to clinic.
The Protective Role of Heat Shock Proteins against Stresses in Animal Breeding
Authors: Liu Sirui , Liu Yinkun , Bao Endong , Tang Shu
Published: July 2024

Heat shock proteins (HSPs) play an important role in all living organisms under stress conditions by acting as molecular chaperones. The expression of different HSPs during stress varies depending on their protective functions and anti-apoptotic activities. The application of HSPs improves the efficiency and decreases the economic cost of animal breeding. By upregulating the expression of HSPs, feed supplements can improve stress tolerance in farm animals. In addition, high expression of HSPs is often a feature of tumor cells, and inhibiting the expression of HSPs is a promising novel method for killing these cells and treating cancers. In the present review, the findings of previous research on the application of HSPs in animal breeding and veterinary medicine are summarized, and the knowledge of the actions of HSPs in animals is briefly discussed.
Mapping of Human Polyomavirus in Renal Cell Carcinoma Tissues
Authors: Mobaraki Ghalib , Shi Shuai , Liu Dan , Smits Kim M. , Severens Kim , Lommen Kim , Rennspiess Dorit , Speel Ernst-Jan M. , Winnepenninckx Véronique , Klufah Faisal , Samarska Iryna , Hausen Axel zur
Published: July 2024

Worldwide, the incidence of renal cell carcinoma (RCC) is rising, accounting for approximately 2% of all cancer diagnoses and deaths. The etiology of RCC is still obscure. Here, we assessed the presence of HPyVs in paraffin-embedded tissue (FFPE) resected tissue from patients with RCC by using different molecular techniques. Fifty-five FFPE tissues from 11 RCC patients were included in this study. Consensus and HPyV-specific primers were used to screen for HPyVs. Both PCR approaches revealed that HPyV is frequently detected in the tissues of RCC kidney resections. A total of 78% (43/55) of the tissues tested were positive for at least one HPyV (i.e., MCPyV, HPyV6, HPyV7, BKPyV, JCPyV, or WUyV). Additionally, 25 tissues (45%) were positive for only one HPyV, 14 (25%) for two HPyVs, 3 (5%) for three HPyVs, and 1 one (1%) tissue specimen was positive for four HPyVs. Eleven (20%) RCC specimens were completely devoid of HPyV sequences. MCPyV was found in 24/55 RCC tissues, HPyV7 in 19, and HPyV6 in 8. The presence of MCPyV and HPyV6 was confirmed by specific FISH or RNA-ISH. In addition, we aimed to confirm HPyV gene expression by IHC. Our results strongly indicate that these HPyVs infect RCC and nontumor tissues, possibly indicating that kidney tissues serve as a reservoir for HPyV latency. Whether HPyVs possibly contribute to the etiopathogenesis of RCC remains to be elucidated.
Impact of Selected Glucagon-like Peptide-1 Receptor Agonists on Serum Lipids, Adipose Tissue, and Muscle Metabolism—A Narrative Review
Authors: Szekeres Zsolt , Nagy Andras , Jahner Kamilla , Szabados Eszter
Published: July 2024

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are novel antihyperglycemic agents. By acting through the central nervous system, they increase satiety and reduce food intake, thus lowering body weight. Furthermore, they increase the secretion of insulin while decreasing the production of glucagon. However, recent studies suggest a more complex metabolic impact through the interaction with various other tissues. In our present review, we aim to provide a summary of the effects of GLP-1 RA on serum lipids, adipose tissue, and muscle metabolism. It has been found that GLP-1 RA therapy is associated with decreased serum cholesterol levels. Epicardial adipose tissue thickness, hepatic lipid droplets, and visceral fat volume were reduced in obese patients with cardiovascular disease. GLP-1 RA therapy decreased the level of proinflammatory adipokines and reduced the expression of inflammatory genes. They have been found to reduce endoplasmic reticulum stress in adipocytes, leading to better adipocyte function and metabolism. Furthermore, GLP-1 RA therapy increased microvascular blood flow in muscle tissue, resulting in increased myocyte metabolism. They inhibited muscle atrophy and increased muscle mass and function. It was also observed that the levels of muscle-derived inflammatory cytokines decreased, and insulin sensitivity increased, resulting in improved metabolism. However, some clinical trials have been conducted on a very small number of patients, which limits the strength of these observations.
The Mitogenomic Landscape of Hexacorallia Corals: Insight into Their Slow Evolution
Authors: Wei Zhanfei , Yang Yang , Meng Lihui , Zhang Nannan , Liu Shanshan , Meng Liang , Li Yang , Shao Changwei
Published: July 2024

The utility of the mitochondrial genomes (mitogenomes) in analyzing the evolutionary history of animals has been proven. Five deep-sea corals (Bathypathes sp.1, Bathypathes sp.2, Schizopathidae 1, Trissopathes sp., and Leiopathes sp.) were collected in the South China Sea (SCS). Initially, the structures and collinearity of the five deep-sea coral mitogenomes were analyzed. The gene arrangements in the five deep-sea coral mitogenomes were similar to those in the order Antipatharia, which evidenced their conservation throughout evolutionary history. Additionally, to elucidate the slow evolutionary rates in Hexacorallia mitogenomes, we conducted comprehensive analyses, including examining phylogenetic relationships, performing average nucleotide identity (ANI) analysis, and assessing GC-skew dissimilarity combining five deep-sea coral mitogenomes and 522 reference Hexacorallia mitogenomes. Phylogenetic analysis using 13 conserved proteins revealed that species clustered together at the order level, and they exhibited interspersed distributions at the family level. The ANI results revealed that species had significant similarities (identity > 85%) within the same order, while species from different orders showed notable differences (identity < 80%). The investigation of the Hexacorallia mitogenomes also highlighted that the GC-skew dissimilarity was highly significant at the order level, but not as pronounced at the family level. These results might be attributed to the slow evolution rate of Hexacorallia mitogenomes and provide evidence of mitogenomic diversity. Furthermore, divergence time analysis revealed older divergence times assessed via mitogenomes compared with nuclear data, shedding light on significant evolutionary events shaping distinct orders within Hexacorallia corals. Those findings provide new insights into understanding the slow evolutionary rates of deep-sea corals in all lineages of Hexacorallia using their mitogenomes.
Endocrine-Disrupting Chemicals: A Looming Threat to Current and Future Generations
Authors: Cortes-Ramirez Sergio A. , Ho Shuk-Mei , Leung Yuet-Kin
Published: July 2024

With rapid modernization, environmental pollutants have become a major concern for human health, contributing to diseases such as asthma, cardiovascular diseases, obesity, infertility, and cancers [...]
Transcriptomic Analysis of the Molecular Mechanism Potential of Grafting—Enhancing the Ability of Oriental Melon to Tolerate Low-Nitrogen Stress
Authors: Zhu Yulei , Sun Ziqing , Wu Hongxi , Cui Caifeng , Meng Sida , Xu Chuanqiang
Published: July 2024

Nitrogen is the primary nutrient for plants. Low nitrogen generally affects plant growth and fruit quality. Melon, as an economic crop, is highly dependent on nitrogen. However, the response mechanism of its self-rooted and grafted seedlings to low-nitrogen stress has not been reported previously. Therefore, in this study, we analyzed the transcriptional differences between self-rooted and grafted seedlings under low-nitrogen stress using fluorescence characterization and RNA-Seq analysis. It was shown that low-nitrogen stress significantly inhibited the fluorescence characteristics of melon self-rooted seedlings. Analysis of differentially expressed genes showed that the synthesis of genes related to hormone signaling, such as auxin and brassinolide, was delayed under low-nitrogen stress. Oxidative stress response, involved in carbon and nitrogen metabolism, and secondary metabolite-related differentially expressed genes (DEGs) were significantly down-regulated. It can be seen that low-nitrogen stress causes changes in many hormonal signals in plants, and grafting can alleviate the damage caused by low-nitrogen stress on plants, ameliorate the adverse effects of nitrogen stress on plants, and help them better cope with environmental stresses.
Orchestrating the Impact of KIR/HLA Interactions on Kidney Transplant
Authors: Loga Luminița-Ioana Iancu , Suharoschi Ramona , Elec Florin Ioan , Chiorean Alin Dan , Elec Alina Daciana , Muntean Adriana Milena , Suciu Mihai Domnuțiu , Antal Oana , Toth Andreea Teodora , Lucaciu Roxana Liana , Hangan Adriana Corina , Drugan Tudor , Matei Horea Vladi , Dican Lucia
Published: July 2024

This study examines the interplay between human leukocyte antigen (HLA) compatibility and killer-cell immunoglobulin-like receptor (KIR) genotypes in influencing kidney transplantation outcomes. Understanding these interactions is crucial for improving graft survival and minimizing rejection risks. We evaluated 84 kidney transplant recipients, dividing them into two groups based on post-transplant outcomes: there were 68 with stable graft function (SGF) and 16 who experienced chronic rejection (CR). Patients were selected based on specific inclusion criteria. HLA mismatches (Class I: HLA-A, -B; Class II: HLA-DR) and KIR genotypes were determined using standard genotyping techniques. Statistical analyses, including logistic regression, were performed to correlate these factors with transplant outcomes. Significant age differences were observed, with younger patients more likely to experience graft rejection, while no significant gender-based differences were noted. A significant correlation was found between Class II mismatches and increased rejection rates, highlighting the importance of HLA-DR compatibility. Further analysis revealed that certain inhibitory KIRs, such as KIR3DL1, were associated with favorable outcomes, suggesting a protective role against graft rejection. These findings were corroborated by evaluating serum creatinine levels over multiple years, serving as a biomarker for renal function post transplant. This study underscores the critical need for meticulous HLA matching and the consideration of KIR genotypes in pre-transplant evaluations to enhance graft survival and minimize rejection risks. Integrating these genetic factors into routine clinical assessments could significantly improve personalized transplant medicine strategies, ultimately enhancing patient outcomes. Further research is needed to explore the underlying mechanisms and validate these findings in larger, diverse populations.
Epigenetic Modifications of Hormonal Signaling Pathways in Plant Drought Response and Tolerance for Sustainable Food Security
Authors: Kaya Cengiz , Uğurlar Ferhat , Adamakis Ioannis-Dimosthenis S.
Published: July 2024

Drought significantly challenges global food security, necessitating a comprehensive understanding of plant molecular responses for effective mitigation strategies. Epigenetic modifications, such as DNA methylation and histone modifications, are key in regulating genes and hormones essential for drought response. While microRNAs (miRNAs) primarily regulate gene expression post-transcriptionally, they can also interact with epigenetic pathways as potential effectors that influence chromatin remodeling. Although the role of miRNAs in epigenetic memory is still being explored, understanding their contribution to drought response requires examining these indirect effects on epigenetic modifications. A key aspect of this exploration is epigenetic memory in drought-adapted plants, offering insights into the transgenerational inheritance of adaptive traits. Understanding the mechanisms that govern the maintenance and erasure of these epigenetic imprints provides nuanced insights into how plants balance stability and flexibility in their epigenomes. A major focus is on the dynamic interaction between hormonal pathways—such as those for abscisic acid (ABA), ethylene, jasmonates, and salicylic acid (SA)—and epigenetic mechanisms. This interplay is crucial for fine-tuning gene expression during drought stress, leading to physiological and morphological adaptations that enhance plant drought resilience. This review also highlights the transformative potential of advanced technologies, such as bisulfite sequencing and CRISPR-Cas9, in providing comprehensive insights into plant responses to water deficit conditions. These technologies pave the way for developing drought-tolerant crops, which is vital for sustainable agriculture.
Apo-Lactoferrin Inhibits the Proteolytic Activity of the 110 kDa Zn Metalloprotease Produced by Mannheimia haemolytica A2
Authors: Ramírez-Rico Gerardo , Ruiz-Mazón Lucero , Reyes-López Magda , Rivillas Acevedo Lina , Serrano-Luna Jesús , de la Garza Mireya
Published: July 2024

Mannheimia haemolytica is the main etiological bacterial agent in ruminant respiratory disease. M. haemolytica secretes leukotoxin, lipopolysaccharides, and proteases, which may be targeted to treat infections. We recently reported the purification and in vivo detection of a 110 kDa Zn metalloprotease with collagenase activity (110-Mh metalloprotease) in a sheep with mannheimiosis, and this protease may be an important virulence factor. Due to the increase in the number of multidrug-resistant strains of M. haemolytica, new alternatives to antibiotics are being explored; one option is lactoferrin (Lf), which is a multifunctional iron-binding glycoprotein from the innate immune system of mammals. Bovine apo-lactoferrin (apo-bLf) possesses many properties, and its bactericidal and bacteriostatic effects have been highlighted. The present study was conducted to investigate whether apo-bLf inhibits the secretion and proteolytic activity of the 110-Mh metalloprotease. This enzyme was purified and sublethal doses of apo-bLf were added to cultures of M. haemolytica or co-incubated with the 110-Mh metalloprotease. The collagenase activity was evaluated using zymography and azocoll assays. Our results showed that apo-bLf inhibited the secretion and activity of the 110-Mh metalloprotease. Molecular docking and overlay assays showed that apo-bLf bound near the active site of the 110-Mh metalloprotease, which affected its enzymatic activity.
Sex-Dependent T Cell Dysregulation in Mice with Diet-Induced Obesity
Authors: Brummer Christina , Singer Katrin , Brand Almut , Bruss Christina , Renner Kathrin , Herr Wolfgang , Pukrop Tobias , Dorn Christoph , Hellerbrand Claus , Matos Carina , Kreutz Marina
Published: July 2024

Obesity is an emerging public health problem. Chronic low-grade inflammation is considered a major promotor of obesity-induced secondary diseases such as cardiovascular and fatty liver disease, type 2 diabetes mellitus, and several cancer entities. Most preliminary studies on obesity-induced immune responses have been conducted in male rodents. Sex-specific differences between men and women in obesity-induced immune dysregulation have not yet been fully outlined but are highly relevant to optimizing prevention strategies for overweight-associated complications. In this study, we fed C57BL/6 female vs. male mice with either standard chow or an obesity-inducing diet (OD). Blood and spleen immune cells were isolated and analyzed by flow cytometry. Lean control mice showed no sex bias in systemic and splenic immune cell composition, whereas the immune responses to obesity were significantly distinct between female and male mice. While immune cell alterations in male OD mice were characterized by a significant reduction in T cells and an increase in myeloid-derived suppressor cells (MDSC), female OD mice displayed preserved T cell numbers. The sex-dependent differences in obesity-induced T cell dysregulation were associated with varying susceptibility to body weight gain and fatty liver disease: Male mice showed significantly more hepatic inflammation and histopathological stigmata of fatty liver in comparison to female OD mice. Our findings indicate that sex impacts susceptibility to obesity-induced T cell dysregulation, which might explain sex-dependent different incidences in the development of obesity-associated secondary diseases. These results provide novel insights into the understanding of obesity-induced chronic inflammation from a sex-specific perspective. Given that most nutrition, exercise, and therapeutic recommendations for the prevention of obesity-associated comorbidities do not differentiate between men and women, the data of this study are clinically relevant and should be taken into consideration in future trials and treatment strategies.
Empagliflozin Prevent High-Glucose Stimulation Inducing Apoptosis and Mitochondria Fragmentation in H9C2 Cells through the Calcium-Dependent Activation Extracellular Signal-Regulated Kinase 1/2 Pathway
Authors: Chen Yung-Lung , Wang Hui-Ting , Lee Wen-Chin , Lin Pei-Ting , Liu Wen-Hao , Hsueh Shu-Kai
Published: July 2024

A previous study showed that high-glucose (HG) conditions induce mitochondria fragmentation through the calcium-mediated activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) in H9C2 cells. This study tested whether empagliflozin could prevent HG-induced mitochondria fragmentation through this pathway. We found that exposing H9C2 cells to an HG concentration decreased cell viability and increased cell apoptosis and caspase-3. Empagliflozin could reverse the apoptosis effect of HG stimulation on H9C2 cells. In addition, the HG condition caused mitochondria fragmentation, which was reduced by empagliflozin. The expression of mitochondria fission protein was upregulated, and fusion proteins were downregulated under HG stimulation. The expression of fission proteins was decreased under empagliflozin treatment. Increased calcium accumulation was observed under the HG condition, which was decreased by empagliflozin. The increased expression of ERK 1/2 under HG stimulation was also reversed by empagliflozin. Our study shows that empagliflozin could reverse the HG condition, causing a calcium-dependent activation of the ERK 1/2 pathway, which caused mitochondria fragmentation in H9C2 cells.
The Increase in the Peroxidase Activity of the Cytochrome C with Substitutions in the Universal Binding Site Is Associated with Changes in the Ability to Interact with External Ligands
Authors: Chertkova Rita V. , Oleynikov Ilya P. , Pakhomov Alexey A. , Sudakov Roman V. , Semenova Marina A. , Arutyunyan Alexander M. , Ptushenko Vasily V. , Kirpichnikov Mikhail P. , Dolgikh Dmitry A. , Vygodina Tatiana V.
Published: July 2024

Cytochrome c (CytC), a one-electron carrier, transfers electrons from complex bc1 to cytochrome c oxidase (CcO) in the electron-transport chain. Electrostatic interaction with the partners, complex bc1 and CcO, is ensured by a lysine cluster near the heme forming the Universal Binding Site (UBS). We constructed three mutant variants of mitochondrial CytC with one (2Mut), four (5Mut), and five (8Mut) Lys->Glu substitutions in the UBS and some compensating Glu->Lys substitutions at the periphery of the UBS for charge compensation. All mutants showed a 4–6 times increased peroxidase activity and accelerated binding of cyanide to the ferric heme of CytC. In contrast, decomposition of the cyanide complex with ferrous CytC, as monitored by magnetic circular dichroism spectroscopy, was slower in mutants compared to WT. Molecular dynamic simulations revealed the increase in the fluctuations of Cα atoms of individual residues of mutant CytC compared to WT, especially in the Ω-loop (70–85), which can cause destabilization of the Fe…S(Met80) coordination link, facilitation of the binding of exogenous ligands cyanide and peroxide, and an increase in peroxidase activity. It was found that only one substitution K72E is enough to induce all these changes, indicating the significance of K72 and the Ω-loop (70–85) for the structure and physiology of mitochondrial CytC. In this work, we also propose using a ferro-ferricyanide buffer as a substrate to monitor the peroxidase activity of CytC. This new approach allows us to determine the rate of peroxidase activity at moderate (200 µM) concentrations of H2O2 and avoid complications of radical formation during the reaction.
Large-Scale Screening of Per- and Polyfluoroalkyl Substance Binding Interactions and Their Mixtures with Nuclear Receptors
Authors: Roy Saptarshi , Moran James , Danasekaran Keerthana , O’Brien Kate , Dakshanamurthy Sivanesan
Published: July 2024

Despite their significant impact, comprehensive screenings and detailed analyses of per- and polyfluoroalkyl substance (PFAS) binding strengths at the orthosteric and allosteric sites of NRs are currently lacking. This study addresses this gap by focusing on the binding interaction analysis of both common and uncommon PFAS with the nuclear receptors (NRs) vitamin D receptor (VDR), peroxisome proliferator-activated receptor gamma (PPARγ), pregnane X receptor (PXR), and estrogen receptor alpha (ERα). Advanced docking simulations were used to screen 9507 PFAS chemicals at the orthosteric and allosteric sites of PPARγ, PXR, VDR, and ERα. All receptors exhibited strong binding interactions at the orthosteric and allosteric site with a significant number of PFAS. We verified the accuracy of the docking protocol through multiple docking controls and validations. A mixture modeling analysis indicates that PFAS can bind in various combinations with themselves and endogenous ligands simultaneously, to disrupt the endocrine system and cause carcinogenic responses. These findings reveal that PFAS can interfere with nuclear receptor activity by displacing endogenous or native ligands by binding to the orthosteric and allosteric sites. The purpose of this study is to explore the mechanisms through which PFAS exert their endocrine-disrupting effects, potentially leading to more targeted therapeutic strategies. Importantly, this study is the first to explore the binding of PFAS at allosteric sites and to model PFAS mixtures at nuclear receptors. Given the high concentration and persistence of PFAS in humans, this study further emphasizes the urgent need for further research into the carcinogenic mechanisms of PFAS and the development of therapeutic strategies that target nuclear receptors.
Antioxidant and Emulsifying Activity of the Exopolymer Produced by Bacillus licheniformis
Authors: Enrique Sánchez-León , Ricardo Amils , Concepción Abrusci
Published: July 2024

The exopolymer (ESPp) was obtained from Bacillus licheniformis IDN-EC, composed of a polyglutamic acid and polyglycerol phosphate chain O-substituted with αGal moieties (αGal/αGlcNH2 3:1 molar ratio) and with a 5000 Da molecular weight. The cytotoxicity activity of EPSp was determined by reducing the MTT (3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide) to formazan on HeLa cells. This EPS did not show cytotoxicity against the tested cell line. The ESPp presented great advantages as an antioxidant with free radical scavenging activities (1,1-diphenyl-2-picryl-hydrazyl radical (DPPH),hydroxyl radical (OH), and superoxide anion (O2−)) (65 ± 1.2%, 98.7 ± 1.9%, and 97 ± 1.7%), respectively. Moreover, EPSp increased the enzyme activity for catalase (CAT) and glutathione peroxidase (GSH-Px) in HeLa cells (CAT, 2.6 ± 0.24 U/mL; and GSH-Px, 0.75 ± 0.3 U/L). The presence of ESPp showed a significant protective effect against H2O2 in the cell line studied, showing great viability (91.8 ± 2.8, 89.9 ± 2.9, and 93.5 ± 3.6%). The EPSp presented good emulsifying activity, only for vegetable oils, olive oil (50 ± 2.1%) and sesame (72 ± 3%). Sesame was effective compared to commercials products, Triton X-100 (52.38 ± 1.6%), Tween 20 (14.29 ± 1.1%), and sodium dodecyl sulphate (SDS) (52.63 ± 1.6%). Furthermore, the EPS produced at 0.6 M has potential for environmental applications, such as the removal of hazardous materials by emulsification whilst resulting in positive health effects such as antioxidant activity and non-toxicity. EPSp is presented as a good exopolysaccharide for various applications.
Advances in Medicine: Photodynamic Therapy
Authors: Aebisher David , Szpara Jakub , Bartusik-Aebisher Dorota
Published: July 2024

Over the past decades, medicine has made enormous progress, revolutionized by modern technologies and innovative therapeutic approaches. One of the most exciting branches of these developments is photodynamic therapy (PDT). Using a combination of light of a specific wavelength and specially designed photosensitizing substances, PDT offers new perspectives in the fight against cancer, bacterial infections, and other diseases that are resistant to traditional treatment methods. In today’s world, where there is a growing problem of drug resistance, the search for alternative therapies is becoming more and more urgent. Imagine that we could destroy cancer cells or bacteria using light, without the need to use strong chemicals or antibiotics. This is what PDT promises. By activating photosensitizers using appropriately adjusted light, this therapy can induce the death of cancer or bacterial cells while minimizing damage to surrounding healthy tissues. In this work, we will explore this fascinating method, discovering its mechanisms of action, clinical applications, and development prospects. We will also analyze the latest research and patient testimonies to understand the potential of PDT for the future of medicine.
Inflammatory Markers Predict Blood Neurofilament Light Chain Levels in Acute COVID-19 Patients
Authors: De Lorenzo Rebecca , Loré Nicola I. , Finardi Annamaria , Mandelli Alessandra , Calesella Federico , Palladini Mariagrazia , Cirillo Daniela M. , Tresoldi Cristina , Ciceri Fabio , Rovere-Querini Patrizia , Manfredi Angelo A. , Mazza Mario G. , Benedetti Francesco , Furlan Roberto
Published: July 2024

Acute coronavirus disease 2019 (COVID-19) is paralleled by a rise in the peripheral levels of neurofilament light chain (NfL), suggesting early nervous system damage. In a cohort of 103 COVID-19 patients, we studied the relationship between the NfL and peripheral inflammatory markers. We found that the NfL levels are significantly predicted by a panel of circulating cytokines/chemokines, including CRP, IL-4, IL-8, IL-9, Eotaxin, and MIP-1ß, which are highly up-regulated during COVID-19 and are associated with clinical outcomes. Our findings show that peripheral cytokines influence the plasma levels of the NfL, suggesting a potential role of the NfL as a marker of neuronal damage associated with COVID-19 inflammation.
Radiation Induced Skin Fibrosis (RISF): Opportunity for Angiotensin II-Dependent Intervention
Authors: Boothe Patricia F. , Kumar Vidya P. , Kong Yali , Wang Kan , Levinson Howard , Mu David , Brown Milton L.
Published: July 2024

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. The primary goal is to offer essential insights in order to better care for and improve the quality of life of cancer survivors who face the risk of developing RISF.
Methylation Modification in Ornamental Plants: Impact on Floral Aroma and Color
Authors: Xie Chenchen , Tian Qingyin , Qiu Hanruo , Wang Rui , Wang Lianggui , Yue Yuanzheng , Yang Xiulian
Published: July 2024

Methylation represents a crucial class of modification that orchestrates a spectrum of regulatory roles in plants, impacting ornamental characteristics, growth, development, and responses to abiotic stress. The establishment and maintenance of methylation involve the coordinated actions of multiple regulatory factors. Methyltransferases play a pivotal role by specifically recognizing and methylating targeted sites, which induces alterations in chromatin structure and gene expression, subsequently influencing the release of volatile aromatic substances and the accumulation of pigments in plant petals. In this paper, we review the regulatory mechanisms of methylation modification reactions and their effects on the changes in aromatic substances and pigments in plant petals. We also explore the potential of methylation modifications to unravel the regulatory mechanisms underlying aroma and color in plant petals. This aims to further elucidate the synthesis, metabolism, and regulatory mechanisms of various methylation modifications related to the aroma and color substances in plant petals, thereby providing a theoretical reference for improving the aroma and color of plant petals.
Genome-Wide Identification and Expression Analysis of SlNRAMP Genes in Tomato under Nutrient Deficiency and Cadmium Stress during Arbuscular Mycorrhizal Symbiosis
Authors: Liu Junli , Bao Xiaoqi , Qiu Gaoyang , Li Hua , Wang Yuan , Chen Xiaodong , Fu Qinglin , Guo Bin
Published: July 2024

Arbuscular mycorrhizal (AM) fungi are well known for enhancing phosphorus uptake in plants; however, their regulating roles in cation transporting gene family, such as natural resistance-associated macrophage protein (NRAMP), are still limited. Here, we performed bioinformatics analysis and quantitative expression assays of tomato SlNRAMP 1 to 5 genes under nutrient deficiency and cadmium (Cd) stress in response to AM symbiosis. These five SlNRAMP members are mainly located in the plasma or vacuolar membrane and can be divided into two subfamilies. Cis-element analysis revealed several motifs involved in phytohormonal and abiotic regulation in their promoters. SlNRAMP2 was downregulated by iron deficiency, while SlNRAMP1, SlNRAMP3, SlNRAMP4, and SlNRAMP5 responded positively to copper-, zinc-, and manganese-deficient conditions. AM colonization reduced Cd accumulation and expression of SlNRAMP3 but enhanced SlNRAMP1, SlNRAMP2, and SlNRMAP4 in plants under Cd stress. These findings provide valuable genetic information for improving tomato resilience to nutrient deficiency and heavy metal stress by developing AM symbiosis.
Sphingosine 1-Phosphate Stimulates ER to Golgi Ceramide Traffic to Promote Survival in T98G Glioma Cells
Authors: Giussani Paola , Brioschi Loredana , Gjoni Enida , Riccitelli Elena , Viani Paola
Published: July 2024

Glioblastoma multiforme is the most common and fatal brain tumor among human cancers. Ceramide (Cer) and Sphingosine 1-phosphate (S1P) have emerged as bioeffector molecules that control several biological processes involved in both cancer development and resistance. Cer acts as a tumor suppressor, inhibiting cancer progression, promoting apoptosis, enhancing immunotherapy and sensitizing cells to chemotherapy. In contrast, S1P functions as an onco-promoter molecule, increasing proliferation, survival, invasiveness, and resistance to drug-induced apoptosis. The pro-survival PI3K/Akt pathway is a recognized downstream target of S1P, and we have previously demonstrated that in glioma cells it also improves Cer transport and metabolism towards complex sphingolipids in glioma cells. Here, we first examined the possibility that, in T98G glioma cells, S1P may regulate Cer metabolism through PI3K/Akt signaling. Our research showed that exogenous S1P increases the rate of vesicular trafficking of Cer from the endoplasmic reticulum (ER) to the Golgi apparatus through S1P receptor-mediated activation of the PI3K/Akt pathway. Interestingly, the effect of S1P results in cell protection against toxicity arising from Cer accumulation in the ER, highlighting the role of S1P as a survival factor to escape from the Cer-generating cell death response.