bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns in Genome-Wide Codon Usage Bias in Representative Species of Lycophytes and Ferns
Authors: Xu Piaoran , Zhang Lijuan , Lu Liping , Zhu Yanli , Gao Dandan , Liu Shanshan
Published: July 2024

The latest research shows that ferns and lycophytes have distinct evolutionary lineages. The codon usage patterns of lycophytes and ferns have not yet been documented. To investigate the gene expression profiles across various plant lineages with respect to codon usage, analyze the disparities and determinants of gene evolution in primitive plant species, and identify appropriate exogenous gene expression platforms, the whole-genome sequences of four distinct species were retrieved from the NCBI database. The findings indicated that Ceratopteris richardii, Adiantum capillus-veneris, and Selaginella moellendorffii exhibited an elevated A/U content in their codon base composition and a tendency to end with A/U. Additionally, S. capillus-veneris had more C/G in its codons and a tendency to end with C/G. The ENC values derived from both ENC-plot and ENC-ratio analyses deviated significantly from the standard curves, suggesting that the codon usage preferences of these four species were primarily influenced by genetic mutations and natural selection, with natural selection exerting a more prominent influence. This finding was further supported by PR2-Plot, neutrality plot analysis, and COA. A combination of RSCU and ENC values was used as a reference criterion to rank the codons and further identify the optimal codons. The study identified 24 high-frequency codons in C. richardii, A. capillus-veneris, and Diphasiastrum complanatum, with no shared optimal codons among the four species. Arabidopsis thaliana and Ginkgo biloba exhibited similar codon preferences to the three species, except for S. moellendorffii. This research offers a theoretical framework at the genomic codon level for investigating the phylogenetic relationships between lycophytes and ferns, shedding light on gene codon optimization and its implications for genetic engineering in breeding.
New Virus Variant Detection Based on the Optimal Natural Metric
Authors: Yu Hongyu , Yau Stephen
Published: July 2024

The highly variable SARS-CoV-2 virus responsible for the COVID-19 pandemic frequently undergoes mutations, leading to the emergence of new variants that present novel threats to public health. The determination of these variants often relies on manual definition based on local sequence characteristics, resulting in delays in their detection relative to their actual emergence. In this study, we propose an algorithm for the automatic identification of novel variants. By leveraging the optimal natural metric for viruses based on an alignment-free perspective to measure distances between sequences, we devise a hypothesis testing framework to determine whether a given viral sequence belongs to a novel variant. Our method demonstrates high accuracy, achieving nearly 100% precision in identifying new variants of SARS-CoV-2 and HIV-1 as well as in detecting novel genera in Orthocoronavirinae. This approach holds promise for timely surveillance and management of emerging viral threats in the field of public health.
Identification and Candidate Gene Evaluation of a Large Fast Neutron-Induced Deletion Associated with a High-Oil Phenotype in Soybean Seeds
Authors: Serson William R. , Gishini Mohammad Fazel Soltani , Stupar Robert M. , Stec Adrian O. , Armstrong Paul R. , Hildebrand David
Published: July 2024

Since the dawn of agriculture, crops have been genetically altered for desirable characteristics. This has included the selection of natural and induced mutants. Increasing the production of plant oils such as soybean (Glycine max) oil as a renewable resource for food and fuel is valuable. Successful breeding for higher oil levels in soybeans, however, usually results in reduced seed protein. A soybean fast neutron population was screened for oil content, and three high oil mutants with minimal reductions in protein levels were found. Three backcross F2 populations derived from these mutants exhibited segregation for seed oil content. DNA was pooled from the high-oil and normal-oil plants within each population and assessed by comparative genomic hybridization. A deletion encompassing 20 gene models on chromosome 14 was found to co-segregate with the high-oil trait in two of the three populations. Eighteen genes in the deleted region have known functions that appear unrelated to oil biosynthesis and accumulation pathways, while one of the unknown genes (Glyma.14G101900) may contribute to the regulation of lipid droplet formation. This high-oil trait can facilitate the breeding of high-oil soybeans without protein reduction, resulting in higher meal protein levels.
Mitochondrial Genome Characteristics Reveal Evolution of Acanthopsetta nadeshnyi (Jordan and Starks, 1904) and Phylogenetic Relationships
Authors: Yang Li-min , Xue Jing-feng , Zhao Xiao-man , Ding Ke , Liu Zhao-wen , Wang Zhou-si-yu , Chen Jian-bing , Huang You-kun
Published: July 2024

In the present study, the mitochondrial genomic characteristics of Acanthopsetta nadeshnyi have been reported and have depicted the phylogenetic relationship among Pleuronectidae. Combined with a comparative analysis of 13 PCGs, the TN93 model was used to review the neutral evolution and habitat evolution catalysis of the mitogenome to verify the distancing and purification selectivity of the mitogenome in Pleuronectidae. At the same time, a species differentiation and classification model based on mitogenome analysis data was established. This study is expected to provide a new perspective on the phylogenetic relationship and taxonomic status of A. nadeshnyi and lay a foundation for further exploration of environmental and biological evolutionary mechanisms.
Early Non-Invasive Prenatal Testing at 6–9 Weeks of Gestation
Authors: Katrachouras Alexandros , Kontos Harry , Konis Kyriacos , Skentou Chara , Makrydimas George
Published: July 2024

Non-invasive prenatal testing (NIPT) is usually performed beyond 10 weeks of gestation, because earlier in pregnancy, the fetal fraction is low, resulting in failure to obtain reliable results. This study aimed to evaluate the clinical performance of NIPT earlier in pregnancy using a method for cell-free DNA (cfDNA) analysis that eliminates the need for polymerase chain reaction (PCR), DNA sequencing, or microarrays (Vanadis® system, PerkinElmer, Waltham, MA, USA). Cell-free DNA was extracted from the maternal plasma of 30 singleton pregnancies at 6–9 weeks of gestation (group 1) and at 11–14 weeks of gestation of the same patients (group 2). The mean crown-rump length (CRL) and gestational age in group A was 16.12 mm and that in group B was 61.45 mm. In group A, results were obtained in all, but one, cases (97%). From the remaining pregnancies, one miscarried at 8 weeks and, therefore, the follow-up NIPT at 12 weeks could not be performed. The fetal sex was diagnosed correctly in the 28 cases that had a successful early test, and the results were in accordance with the examination at 12 weeks. There were no cases of aneuploidies and disomy was diagnosed correctly in all. The “Vanadis” prenatal NIPT assay can successfully be used early during the first trimester at 6–9 weeks of gestation (early NIPT) to identify the fetal sex. Further studies are needed to explore the diagnostic potential for aneuploidies.
Marl Mining Activity and Negative Repercussions for Two Hillside Villages (Northern Italy)
Authors: Luino Fabio , Bonetto Sabrina , Bono Barbara , Comina Cesare , Little William W. , Porfido Sabina , Sassone Paolo , Turconi Laura
Published: July 2024

Coniolo and Brusaschetto, are two small towns located in the Monferrato area of the Alessandria Province, northern Italy. These communities have similar histories related to development and subsequent abandonment of marl quarry activity that began more than a century ago and continued until recently. Quarrying occurred until soil conditions, water infiltration, and excessive depth made cost of extracting and7 lifting material prohibitive. Quarries consisted of tunnels located directly beneath the towns at about 150 m below ground surface. Collapse of the tunnels led to surface subsidence and destruction of overlying homes and much of the municipal infrastructure. In the early Twentieth Century, regulations pertaining to mine and quarry safety were typically deficient, entirely absent, or not followed. Extractive activities of non-energy mineral resources from quarries and mines were and continue to be widespread in Italy, which currently ranks fifth among what are now countries of the European Union (EU). Mining sites are present in all regions of Italy, particularly in the northern part of the country and along coasts, often in areas of geohydrogeological risk. Consequences of anthropogenic pressures that alter the natural environment, such as the physical size of aquifer drawdowns, are linked to issues for a number of extractive sites across the country. This report analyzes historical and technical documents, conducts a geomorphological analysis of hilly slopes surrounding these communities, and examines urban planning and geophysical surveys to determine the impact of subsurface quarrying activities on the overlying ground surface. The study highlights significant problems that are applicable to other localities globally. This research demonstrates: (a) the importance of geological considerations to development and abandonment of mining activity in inhabited areas; (b) the importance of establishing and following safety protocols; and (c) the manner in which economic interests can take precedence over the well-being and lives of those employed to extract resources.
Malaria Severity in the Elimination Continuum: A Retrospective Cohort Study between Beitbridge and Lupane Districts in Zimbabwe, 2021–2023
Authors: Betera Same , Wispriyono Bambang , Nunu Wilfred , Susanna Dewi , Midzi Nicholas , Dhliwayo Patience , Yelda Fitra , Nyamukondiwa Melisa
Published: July 2024

Malaria has created a resurgence crisis in Zimbabwe’s elimination continuum, diverging from global commitment to malaria elimination by 2030. This retrospective cohort study aimed to determine the risk factors associated with severe malaria in the Beitbridge and Lupane districts. Multistage sampling was used to recruit 2414 individuals recorded in the District Health Information Software2 Tracker database. The study used IBM SPSS 29.0.2.0(20) for data analysis, and odds ratios (ORs) to estimate the relative risk (RR; 95% C.I; p < 0.05). The study revealed significant relative risks (p-value < 0.05) for individuals who had no Long-Lasting Insecticidal Nets (Beitbridge 47.4; Lupane 12.3), those who owned but used the LLINs (Beitbridge 24.9; Lupane 7.83), those who slept outdoors during the night (Beitbridge 84.4; Lupane 1.93), and adults (Beitbridge 0.18; Lupane 0.22) compared to the corresponding reference groups. Other factors showed varying RR: sex (Beitbridge 126.1), prompt treatment (Beitbridge 6.78), hosting visitor(s) (Lupane 6.19), and residence (Lupane 1.94) compared to the corresponding reference groups. Risk factor management needs to focus on increasing local awareness of malaria, universal LLINs coverage of indoor and outdoor sleeping spaces, community-based programs on proper and consistent LLIN usage, screening of visitors from malaria-endemic areas, comprehensive entomological activities, mixed malaria interventions in rural hotspots, and future research on local malaria transmission dynamics. While Zimbabwe has the potential to meet the global goal of malaria elimination, success depends on overcoming the risk factors to sustain the gains already made among malaria elimination districts.
Treating Mental Health and Quality of Life in Older Cancer Patients with Cognitive Behavioral Therapy: A Systematic Review and Meta-Analysis
Authors: O’Keefe Kathryn , Chen Meiyan , Lesser Kevin J. , DuVall Adam S. , Dils Alexander T.
Published: July 2024

Background: Cognitive behavioral therapy (CBT) has been successfully utilized in improving mental health (MH) and quality of life (QoL) in the general population, regardless of age. Cancer, which is most frequently diagnosed in older adults, is a debilitating illness that has a detrimental and long-lasting effect on patients’ MH and QoL. While numerous studies have demonstrated CBT’s efficacy, little evidence exists for its role in older cancer patients. This study, using MH and QoL metrics, evaluates the effectiveness of CBT for older adult cancer patients. Methods: Focusing on MH and QoL and an average age of over 60 years old, a final analysis was performed on 17 clinical trials with a total of 124 effect sizes, including 3073 participants receiving CBT. “Metaphor” and “Robumeta” packages in R Statistical Software (version 4.2.2) were used for analysis, which included robust variance estimation (RVE) in intercept-only meta-regression, and univariate meta-regression for moderator analysis. Results: With 17 clinical trials and 124 effect sizes, our results show that CBT moderately improves MH and QoL in cancer patients d = 0.19, 95% CI 0.0166–0.364, p < 0.0399. The delivery format was shown to be a strong moderator of CBT effectiveness with interpersonal technological interventions combined with pre-programmed segments having a very strong treatment effect size (d = 1.7307, 95% CI 1.5244–1.937, p < 0.001). Conclusions: The use of CBT in older adult cancer patients statistically improves MH and QoL, with delivery format and stages of treatment having important roles. Tech-only interpersonal interventions combined with pre-programmed CBT provide an avenue for targeting older adult cancer patients.
Yoga as a Contemplative Practice and Its Contribution to Participatory Self-Knowledge and Student Retention: A Scoping Review of the First-Year Undergraduate Student Transition
Authors: Martin Beverley , Peck Blake , Terry Daniel
Published: July 2024

Background: Contemplative pedagogy, specifically yoga, introduced into the higher education curriculum has the potential to develop and entrain intellectual, emotional, and social development in relation to mental health among university students studying for medical and nursing degrees. The objective of the study is to determine the extent of the current literature on the prevalence of yoga as a contemplative practice that contributes to student well-being and self-knowledge in the first-year transition from high school to university. Methods: As part of the scoping review, CINAHL, EBSCO, Medline, Emerald, Eric, and PsycINFO were searched to identify the prevalence and connection of mind–body courses to student well-being between 2011 and 2022. Screening and selection of studies were based on eligibility criteria and methodological quality assessment. Colaizzi’s method of data analysis enabled the phenomena of interest to be examined and follows the PRISMA for Scoping Reviews (PRISMA-ScR) checklist. Results: Seventeen studies were included with two themes emerging, which include physical practices and training and barriers to success. Conclusion: Yoga is a practice that supports undergraduate students in managing their stressful lives. Due to the experiential nature of yoga the participatory reflective processes established within the physicality of the students provided a framework to cope with the stress and challenges of higher education.
Social Participation and Loneliness in Older Adults in a Rural Australian Context: Individual and Organizational Perspectives
Authors: Wilson Leah , Rice Carrigan , Thompson Sandra
Published: July 2024

A rise in aging populations globally calls attention to factors that influence the well-being and health of older adults, including social participation. In Australia, rural older adults face cultural, social, and physical challenges that place them at risk for isolation. Thus, research surrounding social participation and healthy aging is increasingly relevant, especially in rural areas. This qualitative study in a remote town in Western Australia explores barriers and facilitators to older adults’ social participation. To investigate multiple perspectives, 23 adults aged 50+ and 19 organizations from a rural town were interviewed. A stakeholder reference group was engaged to refine the research design and validate the findings. Feedback from early interviews was used to refine the data collection process, thus enhancing the validity of the findings. Thematic analysis showed that health and mobility issues, inadequate infrastructure, poor sustainability, and cultural tensions commonly impacted social participation. Themes of rural town culture, cultural power dynamics, and rural stoicism were identified as cultural aspects that inhibited participation. Based on results of this study and the supporting literature, recommendations for inclusive activities include supporting community-designed programs, utilizing culturally sensitive language and personnel, expanding services using existing community resources, and diversifying older adults’ roles in existing groups.
Quantitative Assessment of the Inadequate Intake of Macronutrients, Minerals, and Vitamins Associated with Ultra-Processed Food Consumption
Authors: Costa Raiane M. , Oliveira Antonio G. , Torres Karina G. , Souza Anissa M. , Pereira Gabriela S. , Bezerra Ingrid W. L.
Published: July 2024

Studies indicate that ultra-processed food (UP) consumption correlates negatively with essential vitamin and mineral intake and positively with sodium and lipid intake. The objective of this study was to explore the relationship between UP consumption and deviations from nutritional guidelines. An observational, cross-sectional analytical study was conducted on a probability sample of manufacturing workers in the state of Rio Grande do Norte, Brazil. Food consumption was assessed with a 24 h recall survey, and nutrient intake inadequacies were calculated as the difference between individuals’ intake of energy, macronutrients, minerals and vitamins, and the dietary reference intakes for individuals of the same sex and age group, and then analyzed for trends across the percentage contribution of UP to total energy intake with nonparametric multiple regression adjusted for covariates. The study included 921 workers from 33 industries, 55.9% male, with a mean age of 32 years. Overall, the study population exhibited deficits in energy, all macronutrients, and in some micronutrients. With increasing UP contribution to total energy intake, there is a trend towards a greater intake of energy (p < 0.001), total, saturated, monounsaturated, and trans fats (p < 0.001), n6-polyunsaturated fatty acids (p = 0.03), carbohydrates (p < 0.001), calcium (p = 0.008), and manganese (p < 0.001), thiamin (p < 0.001), and vitamin B6 (p = 0.01); however, this comes with a negative consequence in terms of reducing the protein consumption (p = 0.037), fiber (p = 0.035), copper (p = 0.033), and vitamin E (p = 0.002) intake. The results show that correcting energy and micronutrient deficiencies by increasing UP consumption can also lead to a decrease in diet quality.
Novel Leptin-Based Therapeutic Strategies to Limit Synaptic Dysfunction in Alzheimer’s Disease
Authors: Harvey Jenni
Published: July 2024

Accumulation of hyper-phosphorylated tau and amyloid beta (Aβ) are key pathological hallmarks of Alzheimer’s disease (AD). Increasing evidence indicates that in the early pre-clinical stages of AD, phosphorylation and build-up of tau drives impairments in hippocampal excitatory synaptic function, which ultimately leads to cognitive deficits. Consequently, limiting tau-related synaptic abnormalities may have beneficial effects in AD. There is now significant evidence that the hippocampus is an important brain target for the endocrine hormone leptin and that leptin has pro-cognitive properties, as activation of synaptic leptin receptors markedly influences higher cognitive processes including learning and memory. Clinical studies have identified a link between the circulating leptin levels and the risk of AD, such that AD risk is elevated when leptin levels fall outwith the physiological range. This has fuelled interest in targeting the leptin system therapeutically. Accumulating evidence supports this possibility, as numerous studies have shown that leptin has protective effects in a variety of models of AD. Recent findings have demonstrated that leptin has beneficial effects in the preclinical stages of AD, as leptin prevents the early synaptic impairments driven by tau protein and amyloid β. Here we review recent findings that implicate the leptin system as a potential novel therapeutic target in AD.
GPR55 Antagonist CID16020046 Attenuates Obesity-Induced Airway Inflammation by Suppressing Chronic Low-Grade Inflammation in the Lungs
Authors: Son So-Eun , Lee Ye-Ji , Shin Yoon-Jung , Kim Dong-Hyun , Im Dong-Soon
Published: July 2024

GPR55 is a receptor for lysophosphatidylinositols (LPIs) in digestive metabolites. Overnutrition leads to obesity, insulin resistance, and increased LPI levels in the plasma. The involvement of LPIs and GPR55 in adiposity, hepatic steatosis, and atherosclerosis has been previously elucidated. However, the therapeutic efficacy of GPR55 antagonists against obesity-induced airway inflammation has not been studied. The present study investigated whether CID16020046, a selective antagonist of GPR55, could modulate obesity-induced airway inflammation caused by a high-fat diet (HFD) in C57BL/6 mice. Administration of CID16020046 (1 mg/kg) inhibits HFD-induced adiposity and glucose intolerance. Analysis of immune cells in BALF showed that CID16020046 inhibited HFD-induced increase in immune cell infiltration. Histological analysis revealed the HFD induced hypersecretion of mucus and extensive fibrosis in the lungs. CID16020046 inhibited these HFD-induced pathological features. qRT-PCR revealed the HFD-induced increase in the expression of Ifn-γ, Tnf-α, Il-6, Il-13, Il-17A, Il-1β, Nlrp3, and Mpo mRNAs in the lungs. CID16020046 inhibited the HFD-induced increases in these genes. The expression levels of adipokines were regulated by the HFD and CID16020046. AdipoQ in the lungs and gonadal white adipose tissue was decreased by the HFD and reversed by CID16020046. In contrast, Lep was increased by the HFD and suppressed by CID16020046. The findings suggest the potential application of the GPR55 antagonist CID16020046 in obesity-induced airway inflammation.
Expression and Functional Analysis of the Metallothionein and Metal-Responsive Transcription Factor 1 in Phascolosoma esculenta under Zn Stress
Authors: Gu Shenwei , Wang Jingqian , Gao Xinming , Zheng Xuebin , Liu Yang , Chen Yiner , Sun Lianlian , Zhu Junquan
Published: July 2024

Metallothioneins (MTs) are non-enzymatic metal-binding proteins widely found in animals, plants, and microorganisms and are regulated by metal-responsive transcription factor 1 (MTF1). MT and MTF1 play crucial roles in detoxification, antioxidation, and anti-apoptosis. Therefore, they are key factors allowing organisms to endure the toxicity of heavy metal pollution. Phascolosoma esculenta is a marine invertebrate that inhabits intertidal zones and has a high tolerance to heavy metal stress. In this study, we cloned and identified MT and MTF1 genes from P. esculenta (designated as PeMT and PeMTF1). PeMT and PeMTF1 were widely expressed in all tissues and highly expressed in the intestine. When exposed to 16.8, 33.6, and 84 mg/L of zinc ions, the expression levels of PeMT and PeMTF1 in the intestine increased first and then decreased, peaking at 12 and 6 h, respectively, indicating that both PeMT and PeMTF1 rapidly responded to Zn stress. The recombinant pGEX-6p-1-MT protein enhanced the Zn tolerance of Escherichia coli and showed a dose-dependent ABTS free radical scavenging ability. After RNA interference (RNAi) with PeMT and 24 h of Zn stress, the oxidative stress indices (MDA content, SOD activity, and GSH content) and the apoptosis indices (Caspase 3, Caspase 8, and Caspase 9 activities) were significantly increased, implying that PeMT plays an important role in Zn detoxification, antioxidation, and anti-apoptosis. Moreover, the expression level of PeMT in the intestine was significantly decreased after RNAi with PeMTF1 and 24 h of Zn stress, which preliminarily proved that PeMTF1 has a regulatory effect on PeMT. Our data suggest that PeMT and PeMTF1 play important roles in the resistance of P. esculenta to Zn stress and are the key factors allowing P. esculenta to endure the toxicity of Zn.
The Novel A-Type Proanthocyanidin-Rich Phytocomplex SP4™ Acts as a Broad-Spectrum Antiviral Agent against Human Respiratory Viruses
Authors: Sibille Giulia , Mannino Giuseppe , Frasson Ilaria , Pavan Marta , Luganini Anna , Salata Cristiano , Maffei Massimo E. , Gribaudo Giorgio
Published: July 2024

The appearance of new respiratory virus infections in humans with epidemic or pandemic potential has underscored the urgent need for effective broad-spectrum antivirals (BSAs). Bioactive compounds derived from plants may provide a natural source of new BSA candidates. Here, we investigated the novel phytocomplex formulation SP4™ as a candidate direct-acting BSA against major current human respiratory viruses, including coronaviruses and influenza viruses. SP4™ inhibited the in vitro replication of SARS-CoV-2, hCoV-OC43, hCoV-229E, Influenza A and B viruses, and respiratory syncytial virus in the low-microgram range. Using hCoV-OC43 as a representative respiratory virus, most of the antiviral activity of SP4™ was observed to stem primarily from its dimeric A-type proanthocyanidin (PAC-A) component. Further investigations of the mechanistic mode of action showed SP4™ and its PAC-A-rich fraction to prevent hCoV-OC43 from attaching to target cells and exert virucidal activity. This occurred through their interaction with the spike protein of hCoV-OC43 and SARS-CoV-2, thereby interfering with spike functions and leading to the loss of virion infectivity. Overall, these findings support the further development of SP4™ as a candidate BSA of a natural origin for the prevention of human respiratory virus infections.
Synovial Sarcoma of the Kidney: Diagnostic Pitfalls in a Case with Myxoid Monophasic Differentiation and No Epithelial Biomarkers Expression
Authors: Pagliuca Francesca , Carraturo Emma , De Chiara Anna , Vallese Silvia , Giovannoni Isabella , Alaggio Rita , Cannella Lucia , Tafuto Salvatore , Franco Renato
Published: July 2024

Synovial sarcomas are soft tissue tumours of uncertain origin, most commonly found in the upper or lower extremities. They are characterised by distinctive chromosomal rearrangements involving the gene SS18. Synovial sarcomas can occasionally arise also in visceral sites, but retroperitoneal SSs are very unusual. Among them, a few primary renal synovial sarcomas have been described in the scientific literature. Primary renal synovial sarcomas tend to be monophasic and often show cystic changes. Histologically, they can closely resemble other primary kidney tumours, mainly paediatric tumours such as nephroblastoma and clear cell sarcoma of the kidney. In the current work, a primary synovial sarcoma of the kidney with unusual morphological features (extensively myxoid stroma and immunohistochemical positivity for BCOR) is described. Molecular analysis, through targeted RNA sequencing, was of invaluable help in reaching the correct diagnosis. Despite locally advanced disease at presentation, the patient showed an unexpectedly brilliant response to chemotherapy.
Can Isoflavone-Rich Legume Plants Be Useful in the Chemoprevention of Hormone-Dependent Cancers?—A Systematic Review
Authors: Paździora Wojciech , Paśko Paweł , Grabowska Karolina , Galanty Agnieszka
Published: July 2024

Plants from the Fabaceae family are widely distributed around the world, especially in Europe, Asia and North America. They are a rich source of isoflavones, compounds with estrogen-like activity, which are suspected of having a chemopreventive effect against hormone-dependent cancers. Following the PRISMA guidelines, we conducted a systematic review aimed at assessing the impact of Fabaceae plant extracts on hormone-dependent cancer cells and the content of active compounds in plant raw materials. We analyzed the results of 63 articles from in vitro and in vivo studies describing the effect of plant extracts containing isoflavones on cancer cells, along with their anti-inflammatory and antioxidant potential. In the process, we determined the research limitations and future research directions. The collected results indicate the plant species with potentially high contents of phytoestrogens and anti-inflammatory, antioxidant and cytotoxic properties. They point to the potential use of plants in the diet as a source of compounds offering cancer prevention.
Novel Insights into Changes in Gene Expression within the Hypothalamus in Two Asthma Mouse Models: A Transcriptomic Lung–Brain Axis Study
Authors: Bastawy Eslam M. , Eraslan Izel M. , Voglsanger Lara , Suphioglu Cenk , Walker Adam J. , Dean Olivia M. , Read Justin L. , Ziemann Mark , Smith Craig M.
Published: July 2024

Patients with asthma experience elevated rates of mental illness. However, the molecular links underlying such lung–brain crosstalk remain ambiguous. Hypothalamic dysfunction is observed in many psychiatric disorders, particularly those with an inflammatory component due to many hypothalamic regions being unprotected by the blood–brain barrier. To gain a better insight into such neuropsychiatric sequelae, this study investigated gene expression differences in the hypothalamus following lung inflammation (asthma) induction in mice, using RNA transcriptome profiling. BALB/c mice were challenged with either bacterial lipopolysaccharide (LPS, E. coli) or ovalbumin (OVA) allergens or saline control (n = 7 per group), and lung inflammation was confirmed via histological examination of postmortem lung tissue. The majority of the hypothalamus was micro-dissected, and total RNA was extracted for sequencing. Differential expression analysis identified 31 statistically significant single genes (false discovery rate FDR5%) altered in expression following LPS exposure compared to controls; however, none were significantly changed following OVA treatment, suggesting a milder hypothalamic response. When gene sets were examined, 48 were upregulated and 8 were downregulated in both asthma groups relative to controls. REACTOME enrichment analysis suggests these gene sets are involved in signal transduction metabolism, immune response and neuroplasticity. Interestingly, we identified five altered gene sets directly associated with neurotransmitter signaling. Intriguingly, many of these altered gene sets can influence mental health and or/neuroinflammation in humans. These findings help characterize the links between asthma-induced lung inflammation and the brain and may assist in identifying relevant pathways and therapeutic targets for future intervention.
The Effects of Sevoflurane and Aβ Interaction on CA1 Dendritic Spine Dynamics and MEGF10-Related Astrocytic Synapse Engulfment
Authors: Shi Qinfang , Wang Xingxing , Pradhan Arpit Kumar , Fenzl Thomas , Rammes Gerhard
Published: July 2024

General anesthetics may accelerate the neuropathological changes related to Alzheimer’s disease (AD), of which amyloid beta (Aβ)-induced toxicity is one of the main causes. However, the interaction of general anesthetics with different Aβ-isoforms remains unclear. In this study, we investigated the effects of sevoflurane (0.4 and 1.2 maximal alveolar concentration (MAC)) on four Aβ species-induced changes on dendritic spine density (DSD) in hippocampal brain slices of Thy1-eGFP mice and multiple epidermal growth factor-like domains 10 (MEGF10)-related astrocyte-mediated synaptic engulfment in hippocampal brain slices of C57BL/6 mice. We found that both sevoflurane and Aβ downregulated CA1-dendritic spines. Moreover, compared with either sevoflurane or Aβ alone, pre-treatment with Aβ isoforms followed by sevoflurane application in general further enhanced spine loss. This enhancement was related to MEGF10-related astrocyte-dependent synaptic engulfment, only in AβpE3 + 1.2 MAC sevoflurane and 3NTyrAβ + 1.2 MAC sevoflurane condition. In addition, removal of sevoflurane alleviated spine loss in Aβ + sevoflurane. In summary, these results suggest that both synapses and astrocytes are sensitive targets for sevoflurane; in the presence of 3NTyrAβ, 1.2 MAC sevoflurane alleviated astrocyte-mediated synaptic engulfment and exerted a lasting effect on dendritic spine remodeling.
Unraveling the lncRNA-miRNA-mRNA Regulatory Network Involved in Poplar Coma Development through High-Throughput Sequencing
Authors: Song Zihe , Zhang Chenghao , Song Guotao , Wei Hang , Xu Wenlin , Pan Huixin , Ding Changjun , Xu Meng , Zhen Yan
Published: July 2024

Poplar coma, the fluff-like appendages of seeds originating from the differentiated surface cells of the placenta and funicle, aids in the long-distance dispersal of seeds in the spring. However, it also poses hazards to human safety and causes pollution in the surrounding environment. Unraveling the regulatory mechanisms governing the initiation and development of coma is essential for addressing this issue comprehensively. In this study, strand-specific RNA-seq was conducted at three distinct stages of coma development, revealing 1888 lncRNAs and 52,810 mRNAs. The expression profiles of lncRNAs and mRNAs during coma development were analyzed. Subsequently, potential target genes of lncRNAs were predicted through co-localization and co-expression analyses. Integrating various types of sequencing data, lncRNA-miRNA-TF regulatory networks related to the initiation of coma were constructed. Utilizing identified differentially expressed genes encoding kinesin and actin, lncRNA-miRNA-mRNA regulatory networks associated with the construction and arrangement of the coma cytoskeleton were established. Additionally, relying on differentially expressed genes encoding cellulose synthase, sucrose synthase, and expansin, lncRNA-miRNA-mRNA regulatory networks related to coma cell wall synthesis and remodeling were developed. This study not only enhances the comprehension of lncRNA but also provides novel insights into the molecular mechanisms governing the initiation and development of poplar coma.
Piezo 1 and Piezo 2 in the Chemosensory Organs of Zebrafish (Danio rerio)
Authors: Aragona Marialuisa , Mhalhel Kamel , Cometa Marzio , Franco Gianluca Antonio , Montalbano Giuseppe , Guerrera Maria Cristina , Levanti Maria , Laurà Rosaria , Abbate Francesco , Vega José A. , Germanà Antonino
Published: July 2024

The ion channels Piezo 1 and Piezo 2 have been identified as membrane mechano-proteins. Studying mechanosensitive channels in chemosensory organs could help in understanding the mechanisms by which these channels operate, offering new therapeutic targets for various disorders. This study investigates the expression patterns of Piezo proteins in zebrafish chemosensory organs. For the first time, Piezo protein expression in adult zebrafish chemosensory organs is reported. In the olfactory epithelium, Piezo 1 immunolabels kappe neurons, microvillous cells, and crypt neurons, while Calretinin is expressed in ciliated sensory cells. The lack of overlap between Piezo 1 and Calretinin confirms Piezo 1’s specificity for kappe neurons, microvillous cells, and crypt neurons. Piezo 2 shows intense immunoreactivity in kappe neurons, one-ciliated sensory cells, and multi-ciliated sensory cells, with overlapping Calretinin expression, indicating its olfactory neuron nature. In taste buds, Piezo 1 immunolabels Merkel-like cells at the bases of cutaneous and pharyngeal taste buds and the light and dark cells of cutaneous and oral taste buds. It also marks the dark cells of pharyngeal taste buds and support cells in oral taste buds. Piezo 2 is found in the light and dark cells of cutaneous and oral taste buds and isolated chemosensory cells. These findings provide new insights into the distribution of Piezo channels in zebrafish chemosensory organs, enhancing our understanding of their sensory processing and potential therapeutic applications.
Antiviral Drug Discovery
Authors: Zhou Zhenzhen , Liu Xinyong , Kang Dongwei
Published: July 2024

A vast and painful price has been paid in the battle against viruses in global health [...]
Is Component-Specific Antibody Testing Sufficient to Replace the Oral Food Challenge in the Diagnostics of Peanut-Sensitized Children? A Proof-of-Concept Study
Authors: Łyżwa Klementyna , Prasek Klaudia , Krupa-Łaska Anna , Zielińska Joanna , Krejner-Bienias Alicja , Chojnowska-Wójtowicz Magdalena , Zagórska Wioletta , Kulus Marek , Grzela Adam , Grzela Tomasz , Grzela Katarzyna
Published: July 2024

(1) Peanut allergy is associated with high risk of anaphylaxis which could be prevented by oral immunotherapy. Patients eligible for immunotherapy are selected on the basis of a food challenge, although currently the assessment of antibodies against main peanut molecules (Ara h 1, 2, 3 and 6) is thought to be another option. (2) The current study assessed the relationship between the mentioned antibodies, challenge outcomes, skin tests and some other parameters in peanut-sensitized children. It involved 74 children, divided into two groups, based on their response to a food challenge. (3) Both groups differed in results of skin tests, levels of component-specific antibodies and peanut exposure history. The antibody levels were then used to calculate thresholds for prediction of challenge results or symptom severity. While the antibody-based challenge prediction revealed statistical significance, it failed in cases of severe symptoms. Furthermore, no significant correlation was observed between antibody levels, symptom-eliciting doses and the risk of severe anaphylaxis. Although in some patients it could result from interference with IgG4, the latter would not be a universal explanation of this phenomenon. (4) Despite some limitations, antibody-based screening may be an alternative to the food challenge, although its clinical relevance still requires further studies.
Metabolic and Transcriptional Analysis Reveals Flavonoid Involvement in the Drought Stress Response of Mulberry Leaves
Authors: Chen Guo , Li Dong , Yao Pei , Chen Fengyao , Yuan Jianglian , Ma Bi , Yang Zhen , Ding Biyue , He Ningjia
Published: July 2024

Abiotic stress, especially drought stress, poses a significant threat to terrestrial plant growth, development, and productivity. Although mulberry has great genetic diversity and extensive stress-tolerant traits in agroforestry systems, only a few reports offer preliminary insight into the biochemical responses of mulberry leaves under drought conditions. In this study, we performed a comparative metabolomic and transcriptomic analysis on the “drooping mulberry” (Morus alba var. pendula Dippel) under PEG-6000-simulated drought stress. Our research revealed that drought stress significantly enhanced flavonoid accumulation and upregulated the expression of phenylpropanoid biosynthetic genes. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) content were elevated. In vitro enzyme assays and fermentation tests indicated the involvement of flavonol synthase/flavanone 3-hydroxylase (XM_010098126.2) and anthocyanidin 3-O-glucosyltransferase 5 (XM_010101521.2) in the biosynthesis of flavonol aglycones and glycosides, respectively. The recombinant MaF3GT5 protein was found to recognize kaempferol, quercetin, and UDP-glucose as substrates but not 3-/7-O-glucosylated flavonols and UDP-rhamnose. MaF3GT5 is capable of forming 3-O- and 7-O-monoglucoside, but not di-O-glucosides, from kaempferol. This implies its role as a flavonol 3, 7-O-glucosyltransferase. The findings from this study provided insights into the biosynthesis of flavonoids and could have substantial implications for the future diversified utilization of mulberry.
New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Veno-Arterial Extracorporeal Membrane Oxygenation in the Rat
Authors: Edinger Fabian , Holtz Lena , Schmidt Götz , Schneck Emmanuel , Zajonz Thomas , Sander Michael , Koch Christian
Published: July 2024

Despite significant efforts toward improving therapy for septic shock, mortality remains high. Applying veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) in this context remains controversial. Since the cannulation of the femoral artery for V-A ECMO return leads to lower body hyperoxia, this study investigated the impact of V-A ECMO therapy on the intestinal and hepatic microcirculation during septic shock in a rodent model. Thirty male Lewis rats were randomly assigned to receive V-A ECMO therapy with low (60 mL/kg/min) or high (90 mL/kg/min) blood flow or a sham procedure. Hemodynamic data were collected through a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by intravenous administration of lipopolysaccharide (1 mg/kg). The rats received lung-protective ventilation during V-A ECMO therapy. The hepatic and intestinal microcirculation was measured by micro-lightguide spectrophotometry after median laparotomy for two hours. Systemic and pulmonary inflammation was detected via enzyme-linked immunosorbent assays (ELISA) of the plasma and bronchoalveolar lavage (BAL), respectively, measuring tumor necrosis factor-alpha (TNF-α), interleukins 6 (IL-6) and 10 (IL-10), and C-X-C motif ligands 2 (CXCL2) and 5 (CXCL5). Oxygen saturation and relative hemoglobin concentration were reduced in the hepatic and intestinal microcirculation during V-A ECMO therapy, independent of the blood flow rate. Further, rats treated with V-A ECMO therapy also presented elevated systolic, diastolic, and mean arterial blood pressure and increased stroke volume, cardiac output, and left ventricular end-diastolic volume. However, left ventricular end-diastolic pressure was only elevated during high-flow V-A ECMO therapy. Blood gas analysis revealed a dilutional anemia during V-A ECMO therapy. ELISA analysis showed an elevated plasma CXCL2 concentration only during high-flow V-A ECMO therapy and elevated BAL CXCL2 and CXCL5 concentrations only during low-flow V-A ECMO therapy. Rats undergoing V-A ECMO therapy exhibited impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Increased pulmonary inflammation was detected only during low-flow V-A ECMO therapy in septic shock.
Investigation of Phosphatidylcholine by MALDI Imaging Mass Spectrometry in Normal and IVF Early-Stage Embryos
Authors: Gitta Stefánia , Szabó Éva , Sulc Alexandra , Czétány Péter , Máté Gábor , Balló András , Csabai Tímea , Szántó Árpád , Márk László
Published: July 2024

The receptive phase of the uterus is marked by structural and functional maturation of the endometrium. During this limited time span, the blastocyst competency is superimposed on the receptive endometrium. It is a well-known fact that lipid signalling in early-stage pregnancy has a crucial role in successful embryogenesis. In our study, CD-1 mouse uteri after normal and in vitro fertilization (IVF) were investigated at 6.5, 8.5, and 10.5 days of pregnancy. Matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry and liquid chromatography coupled tandem mass spectrometry were used for identification of phosphatidylcholine (PC) lipid structures. In the embryonal tissues, PC 32:0 and PC 34:0 were increased, while in the antemesometrial (AM) decidua the two 20:4-containing PCs, PC 36:4 and PC 38:4 were increased. In transferred uterus samples, higher expressions of PC 34:0, PC 34:1, PC 34:2, PC 36:1, and PC 36:2 in mesometrial decidua were seen, whereas the two 20:4-containing PCs, PC 36:4 and PC 38:4 showed increased expression in the AM and lateral decidua. This paper shows a significant spatio-temporal change in lipid metabolism during IVF procedures for the first time.
Tofacitinib Treatment Suppresses CD4+ T-Cell Activation and Th1 Response, Contributing to Protection against Staphylococcal Toxic Shock
Authors: Jarneborn Anders , Hu Zhicheng , Deshmukh Meghshree , Kopparapu Pradeep Kumar , Jin Tao
Published: July 2024

Staphylococcal toxic shock syndrome (STSS) is a rare, yet potentially fatal disease caused by Staphylococcus aureus (S. aureus) enterotoxins, known as superantigens, which trigger an intense immune response. Our previous study demonstrated the protective effect of tofacitinib against murine toxin-induced shock and a beneficial effect against S. aureus sepsis. In the current study, we examined the effects of tofacitinib on T-cell response in peripheral blood using a mouse model of enterotoxin-induced shock. Our data revealed that tofacitinib suppresses the activation of both CD4+ and CD8+ T cells in peripheral blood. Furthermore, both gene and protein levels of Th1 cytokines were downregulated by tofacitinib treatment in mice with enterotoxin-induced shock. Importantly, we demonstrated that CD4+ cells, but not CD8+ cells, are pathogenic in mice with enterotoxin-induced shock. In conclusion, our findings suggest that tofacitinib treatment suppresses CD4+ T-cell activation and Th1 response, thereby aiding in protection against staphylococcal toxic shock in mice. This insight may guide the future development of novel therapies for STSS.
Innovative Strategies to Combat 5-Fluorouracil Resistance in Colorectal Cancer: The Role of Phytochemicals and Extracellular Vesicles
Authors: Barathan Muttiah , Zulpa Ahmad Khusairy , Ng Sook Luan , Lokanathan Yogeswaran , Ng Min Hwei , Law Jia Xian
Published: July 2024

Colorectal cancer (CRC) is a significant public health challenge, with 5-fluorouracil (5-FU) resistance being a major obstacle to effective treatment. Despite advancements, resistance to 5-FU remains formidable due to complex mechanisms such as alterations in drug transport, evasion of apoptosis, dysregulation of cell cycle dynamics, tumor microenvironment (TME) interactions, and extracellular vesicle (EV)-mediated resistance pathways. Traditional chemotherapy often results in high toxicity, highlighting the need for alternative approaches with better efficacy and safety. Phytochemicals (PCs) and EVs offer promising CRC therapeutic strategies. PCs, derived from natural sources, often exhibit lower toxicity and can target multiple pathways involved in cancer progression and drug resistance. EVs can facilitate targeted drug delivery, modulate the immune response, and interact with the TME to sensitize cancer cells to treatment. However, the potential of PCs and engineered EVs in overcoming 5-FU resistance and reshaping the immunosuppressive TME in CRC remains underexplored. Addressing this gap is crucial for identifying innovative therapies with enhanced efficacy and reduced toxicities. This review explores the multifaceted mechanisms of 5-FU resistance in CRC and evaluates the synergistic effects of combining PCs with 5-FU to improve treatment efficacy while minimizing adverse effects. Additionally, it investigates engineered EVs in overcoming 5-FU resistance by serving as drug delivery vehicles and modulating the TME. By synthesizing the current knowledge and addressing research gaps, this review enhances the academic understanding of 5-FU resistance in CRC, highlighting the potential of interdisciplinary approaches involving PCs and EVs for revolutionizing CRC therapy. Further research and clinical validation are essential for translating these findings into improved patient outcomes.