bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Transformation of Inefficient Camellia oleifera Plantation on Soil Quality and Fungal Communities
Authors: Tan Zhiming , Liu Ting , Ning Chen , Lin Xianying , Liu Xun , Jiang Maoping , Liu Shuguang , Yan Wende
Published: March 2024

Camellia oleifera, a key economic forestry species in southern China, struggles with low productivity due to suboptimal planting management. Recently, transforming old or unadopted varieties of C. oleifera plantations has been recognized as a means to enhance economic benefits and production. However, the impact of these transformations on soil properties and fungal communities has received little attention. In this study, we targeted pre-renewal old C. oleifera and post-renewal young C. oleifera, Pinus massoniana, and Cunninghamia lanceolata. Through field sampling and soil physicochemical property analysis, we developed a soil quality evaluation system that effectively analyzes fungal community structures and identifies key arbuscular mycorrhizal fungi (AMF) species for soil health. We found that the soil quality evaluation system for this region comprises pH, TK, AK, NO3−, PO4− BG, ACP, F.simpson, AMF.shannon, and AMF.ace, which collectively indicated significant improvements in soil quality following transformation. Notably, the nutritional characteristics of the dominant fungal communities underwent marked changes, with an increase in pathogenic fungi in young C. oleifera and an expansion of ectomycorrhizal fungi in P. massoniana forests. The AMF communities in all four types of forest exhibited aggregation, and Scutellospora and Diversispora emerged as key species in the AMF community of C. oleifera. Additionally, Mortierella and Trichoderma were found to enhance plant resistance to pathogenic fungi. This study demonstrates that forestland transformation positively impacts soil quality and fungal community structure in C. oleifera, which provides valuable insights for future soil management in the region, both in terms of soil quality evaluation and fungal conservation.
Prediction and Transition of Vegetation Vulnerability in the Mara River Basin under Different Shared Socio-Economic Pathways (SSPs), East Africa
Authors: Zhu Wanyi , Zhang Zhenke , Feng Shouming , Ren Hang
Published: March 2024

The Mara River basin (MRB) has a world-famous ecosystem, but the vegetation has been damaged due to economic development in recent years, and there is little known about the area that will experience severe vegetation damage in the future. Based on the vegetation vulnerability system, principal component analysis, and three Shared Socio-Economic Pathways (SSP1-2.6, SSP2-4.5, SSP5-8.5), vegetation vulnerability was calculated for the base period (2010–2019), near future period (2020–2059) and distinct future period (2060–2099) in the MRB. The spatial cluster of vegetation vulnerability was revealed by spatial correlation analysis, and the transition of vegetation vulnerability of different periods was analyzed by stochastic matrix. The results showed that for all periods, the vulnerability showed a high–high cluster in the east, and a low–low cluster midstream and downstream. From the stochastic matrix, the area of high vulnerability increased the least under the SSP1-2.6, while it increased the most under the SSP5-8.5. The vegetation vulnerability upstream increased the most from the base period to the near future period and distinct future period in the MRB. By comparing the vegetation vulnerability under different scenarios and pointing out the areas with the highest vulnerability increase, this study can better provide comprehensive decision-making for vegetation protection in the MRB.
Estimation of Forest Canopy Fuel Moisture Content in Dali Prefecture by Combining Vegetation Indices and Canopy Radiative Transfer Models from MODIS Data
Authors: Yang Kun , Tang Bo-Hui , Fu Wei , Zhou Wei , Fu Zhitao , Fan Dong
Published: March 2024

Forest canopy fuel moisture content (FMC) is a critical factor in assessing the vulnerability of a specific area to forest fires. The conventional FMC estimation method, which relies on look-up tables and loss functions, cannot to elucidate the relationship between FMC and simulated data from look-up tables. This study proposes a novel approach for estimating FMC by combining enhanced vegetation index (EVI) and normalized difference moisture index (NDMI). The method employs the PROSAIL + PROGeoSAIL two-layer coupled radiation transfer model to simulate the vegetation index, the water index, and the FMC value, targeting the prevalent double-layer structure in the study area’s vegetation distribution. Additionally, a look-up table is constructed through numerical analysis to investigate the relationships among vegetation indices, water indices, and FMC. The results reveal that the polynomial equations incorporating vegetation and water indices as independent variables exhibit a strong correlation with FMC. Utilizing the EVI–NDMI joint FMC estimation method enables the direct estimation of FMC. The collected samples from Dali were compared with the estimated values, revealing that the proposed method exhibits superior accuracy (R2 = 0.79) in comparison with conventional FMC estimation methods. In addition, we applied this method to estimate the FMC in the Chongqing region one week before the 2022 forest fire event, revealing a significant decreasing trend in regional FMC leading up to the fire outbreak, highlighting its effectiveness in facilitating pre-disaster warnings.
Cooked Rice Textural Properties and Starch Physicochemical Properties from New Hybrid Rice and Their Parents
Authors: Gao Yan , Zhang Lin , Chen Weiwei , Zhou Weiyong , Deng Guofu , Dai Gaoxing , Bao Jinsong
Published: March 2024

Although great progress has been made in the development of hybrid rice with increased yield, challenges for the improvement of grain quality still remain. In this study, the textural properties of cooked rice and physicochemical characteristics of starch were investigated for 29 new hybrid rice derived from 5 sterile and 11 restorer rice lines. Except for one sterile line Te A (P1) with high apparent amylose content (AAC) (26.9%), all other parents exhibited a low AAC. Gui 263 demonstrated the highest AAC (20.6%) among the restorer lines, so the Te A/Gui 263 hybrid displayed the highest AAC (23.1%) among all the hybrid rice. The mean AAC was similar between sterile, restorer lines and hybrid rice. However, the mean hardness of cooked rice and gels of sterile lines were significantly higher than that of restorer lines and hybrid rice (p < 0.05). Pasting temperature and gelatinization temperatures were significantly higher in the hybrids than in the restorer lines (p < 0.05). Cluster analysis based on the physicochemical properties divided the parents and hybrid rice into two major groups. One group included P1 (Te A), P12 and P14 and three hybrid rice derived from P1, while the other group, including 39 rice varieties, could be further divided into three subgroups. AAC showed significant correlation with many parameters, including peak viscosity, hot peak viscosity, cold peak viscosity, breakdown, setback, onset temperature, peak temperature, conclusion temperature, enthalpy of gelatinization, gel hardness and cooked rice hardness (p < 0.05). Principal component analysis revealed that the first component, comprised of the AAC, peak viscosity, breakdown, setback, onset temperature, peak temperature, conclusion temperature and gel hardness, explained 44.1% of variance, suggesting AAC is the most important factor affecting the grain quality of hybrid rice. Overall, this study enables targeted improvements to key rice grain quality attributes, particularly AAC and textural properties, that will help to develop superior rice varieties.
Regulation of Hair Follicle Growth and Development by Different Alternative Spliceosomes of FGF5 in Rabbits
Authors: Sun Shaoning , Zhao Bohao , Li Jiali , Zhang Xiyu , Yao Shuyu , Bao Zhiyuan , Cai Jiawei , Yang Jie , Chen Yang , Wu Xinsheng
Published: March 2024

This study investigated the regulatory effect of alternative spliceosomes of the fibroblast growth factor 5 (FGF5) gene on hair follicle (HF) growth and development in rabbits. The FGF5 alternative spliceosomes (called FGF5-X1, FGF5-X2, FGF5-X3) were cloned. The overexpression vector and siRNA of spliceosomes were transfected into dermal papilla cells (DPCs) to analyze the regulatory effect on DPCs. The results revealed that FGF5-X2 and FGF5-X3 overexpression significantly decreased LEF1 mRNA expression (p < 0.01). FGF5-X1 overexpression significantly reduced CCND1 expression (p < 0.01). FGF5-X1 and FGF5-X2 possibly downregulated the expression level of FGF2 mRNA (p < 0.05), and FGF5-X3 significantly downregulated the expression level of FGF2 mRNA (p < 0.01). The FGF5 alternative spliceosomes significantly downregulated the BCL2 mRNA expression level in both cases (p < 0.01). FGF5-X1 and FGF5-X2 significantly increased TGFβ mRNA expression (p < 0.01). All three FGF5 alternative spliceosomes inhibited DPC proliferation. In conclusion, the expression profile of HF growth and development-related genes can be regulated by FGF5 alternative spliceosomes, inhibiting the proliferation of DPCs and has an influence on the regulation of HF growth in rabbits. This study provides insights to further investigate the mechanism of HF development in rabbits via FGF5 regulation.
Reconstruction of Metabolic–Protein Interaction Integrated Network of Eriocheir sinensis and Analysis of Ecdysone Synthesis
Authors: Hao Tong , Song Zhentao , Zhang Mingzhi , Zhang Lingrui , Yang Jiarui , Li Jingjing , Sun Jinsheng
Published: March 2024

Integrated networks have become a new interest in genome-scale network research due to their ability to comprehensively reflect and analyze the molecular processes in cells. Currently, none of the integrated networks have been reported for higher organisms. Eriocheir sinensis is a typical aquatic animal that grows through ecdysis. Ecdysone has been identified to be a crucial regulator of ecdysis, but the influence factors and regulatory mechanisms of ecdysone synthesis in E. sinensis are still unclear. In this work, the genome-scale metabolic network and protein–protein interaction network of E. sinensis were integrated to reconstruct a metabolic–protein interaction integrated network (MPIN). The MPIN was used to analyze the influence factors of ecdysone synthesis through flux variation analysis. In total, 236 integrated reactions (IRs) were found to influence the ecdysone synthesis of which 16 IRs had a significant impact. These IRs constitute three ecdysone synthesis routes. It is found that there might be alternative pathways to obtain cholesterol for ecdysone synthesis in E. sinensis instead of absorbing it directly from the feeds. The MPIN reconstructed in this work is the first integrated network for higher organisms. The analysis based on the MPIN supplies important information for the mechanism analysis of ecdysone synthesis in E. sinensis.
Genetic Background of Blood β-Hydroxybutyrate Acid Concentrations in Early-Lactating Holstein Dairy Cows Based on Genome-Wide Association Analyses
Authors: Wang Yueqiang , Wang Zhenyu , Liu Wenhui , Xie Shuoqi , Ren Xiaoli , Yan Lei , Liang Dong , Gao Tengyun , Fu Tong , Zhang Zhen , Huang Hetian
Published: March 2024

Ketosis is a common metabolic disorder in the early lactation of dairy cows. It is typically diagnosed by measuring the concentration of β-hydroxybutyrate (BHB) in the blood. This study aimed to estimate the genetic parameters of blood BHB and conducted a genome-wide association study (GWAS) based on the estimated breeding value. Phenotypic data were collected from December 2019 to August 2023, comprising blood BHB concentrations in 45,617 Holstein cows during the three weeks post-calving across seven dairy farms. Genotypic data were obtained using the Neogen Geneseek Genomic Profiler (GGP) Bovine 100 K SNP Chip and GGP Bovine SNP50 v3 (Illumina Inc., San Diego, CA, USA) for genotyping. The estimated heritability and repeatability values for blood BHB levels were 0.167 and 0.175, respectively. The GWAS result detected a total of ten genome-wide significant associations with blood BHB. Significant SNPs were distributed in Bos taurus autosomes (BTA) 2, 6, 9, 11, 13, and 23, with 48 annotated candidate genes. These potential genes included those associated with insulin regulation, such as INSIG2, and those linked to fatty acid metabolism, such as HADHB, HADHA, and PANK2. Enrichment analysis of the candidate genes for blood BHB revealed the molecular functions and biological processes involved in fatty acid and lipid metabolism in dairy cattle. The identification of novel genomic regions in this study contributes to the characterization of key genes and pathways that elucidate susceptibility to ketosis in dairy cattle.
Innovations in Medicine: Exploring ChatGPT’s Impact on Rare Disorder Management
Authors: Zampatti Stefania , Peconi Cristina , Megalizzi Domenica , Calvino Giulia , Trastulli Giulia , Cascella Raffaella , Strafella Claudia , Caltagirone Carlo , Giardina Emiliano
Published: March 2024

Artificial intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use, ChatGPT holds a prominent position, using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for generating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT integration, with pilot studies and trials revealing each field’s potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex datasets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.
Genome-Wide Identification, Characterization, and Expression Analysis of the HD-Zip Gene Family in Lagerstroemia for Regulating Plant Height
Authors: Lin Hang , Jiang Xinqiang , Qian Cheng , Zhang Yue , Meng Xin , Liu Nairui , Li Lulu , Wang Jingcai , Ju Yiqian
Published: March 2024

The Homeodomain leucine zipper (HD-Zip) family of transcription factors is crucial in helping plants adapt to environmental changes and promoting their growth and development. Despite research on the HD-Zip family in various plants, studies in Lagerstroemia (crape myrtle) have not been reported. This study aimed to address this gap by comprehensively analyzing the HD-Zip gene family in crape myrtle. This study identified 52 HD-Zip genes in the genome of Lagerstroemia indica, designated as LinHDZ1-LinHDZ52. These genes were distributed across 22 chromosomes and grouped into 4 clusters (HD-Zip I-IV) based on their phylogenetic relationships. Most gene structures and motifs within each cluster were conserved. Analysis of protein properties, gene structure, conserved motifs, and cis-acting regulatory elements revealed diverse roles of LinHDZs in various biological contexts. Examining the expression patterns of these 52 genes in 6 tissues (shoot apical meristem, tender shoot, and mature shoot) of non-dwarf and dwarf crape myrtles revealed that 2 LinHDZs (LinHDZ24 and LinHDZ14) and 2 LinHDZs (LinHDZ9 and LinHDZ35) were respectively upregulated in tender shoot of non-dwarf crape myrtles and tender and mature shoots of dwarf crape myrtles, which suggested the important roles of these genes in regulate the shoot development of Lagerstroemia. In addition, the expression levels of 2 LinHDZs (LinHDZ23 and LinHDZ34) were significantly upregulated in the shoot apical meristem of non-dwarf crape myrtle. These genes were identified as key candidates for regulating Lagerstroemia plant height. This study enhanced the understanding of the functions of HD-Zip family members in the growth and development processes of woody plants and provided a theoretical basis for further studies on the molecular mechanisms underlying Lagerstroemia plant height.
Cytogenetic Analysis of Satellitome of Madagascar Leaf-Tailed Geckos
Authors: Yurchenko Alona , Pšenička Tomáš , Mora Pablo , Ortega Juan Alberto Marchal , Baca Antonio Sánchez , Rovatsos Michail
Published: March 2024

Satellite DNA (satDNA) consists of sequences of DNA that form tandem repetitions across the genome, and it is notorious for its diversity and fast evolutionary rate. Despite its importance, satDNA has been only sporadically studied in reptile lineages. Here, we sequenced genomic DNA and PCR-amplified microdissected W chromosomes on the Illumina platform in order to characterize the monomers of satDNA from the Henkel’s leaf-tailed gecko U. henkeli and to compare their topology by in situ hybridization in the karyotypes of the closely related Günther’s flat-tail gecko U. guentheri and gold dust day gecko P. laticauda. We identified seventeen different satDNAs; twelve of them seem to accumulate in centromeres, telomeres and/or the W chromosome. Notably, centromeric and telomeric regions seem to share similar types of satDNAs, and we found two that seem to accumulate at both edges of all chromosomes in all three species. We speculate that the long-term stability of all-acrocentric karyotypes in geckos might be explained from the presence of specific satDNAs at the centromeric regions that are strong meiotic drivers, a hypothesis that should be further tested.
Relation between Photogrammetry and Spinal Mouse for Lumbopelvic Assessment in Adolescents with Thoracic Kyphosis
Authors: Belli Guido , Russo Luca , Mauro Mario , Toselli Stefania , Maietta Latessa Pasqualino
Published: March 2024

The evaluation of the lumbopelvic region is a crucial point during postural assessment in childhood and adolescence. Photogrammetry (PG) and Spinal Mouse (SM) are two of the most debated tools to properly analyze postural alignment and avoid misleading data. This study aims to find out the best linear regression model that could relate the analytic measurements of the SM with one or more PG parameters in adolescents with kyphotic postures. Thirty-nine adolescents (female = 35.9%) with structural and non-structural kyphosis were analyzed (13.2 ± 1.8 years; 1.59 ± 0.12 m; 47.6 ± 11.8 kg) using the SM and PG on the sagittal plane in a standing and forward-bending position, allowing for the measurement of body vertical inclination, lumbar and pelvic alignment, trunk flexion, sacral inclination during bending, and hip position during bending. Lordosis lumbar angles (SM) were significantly (r = −0.379, r = −0.328) correlated with the SIPS-SIAS angle (PG) during upright standing, while in the bending position, the highest correlation appeared among the sacral–hip (SM) and the sacral tangent (ST_PG; r = −0.72) angles. The stepwise backward procedure was assessed to estimate the SM variability in the bending and standing positions. Only in the bending position did the linear regression model reach high goodness-of-fit values with two regressors (ST_PG η2=0.504, BMI η2=0.252; adjusted- R2 =0.558, p < 0.001, CCC = 0.972, r = 0.763). Despite gold-standard methods reducing error evaluation, physicians and kinesiologists may consider photogrammetry as a good method for spinal curve prediction.
Ophthalmic Manifestations in Patients with Blood Malignancies
Authors: Rossi Costanza , Buizza Alessandro , Alessio Giuseppe , Borselli Massimiliano , Taloni Andrea , Carnevali Adriano , Carnovale Scalzo Giovanna , Lucisano Andrea , Scorcia Vincenzo , Giannaccare Giuseppe
Published: March 2024

Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 and examines the common ocular complications associated with blood cancers. Ocular complications from primary disease include mass effects from ocular adnexal lymphomas and intraocular lymphomas, with B-cell lymphomas accounting for 95% of primary ocular presentations. Secondary disease involvement from systemic hematological malignancies can lead to a wide range of ocular manifestations, such as leukemic retinopathy. Furthermore, toxicity from antineoplastic therapies and ocular graft versus host disease (oGVHD) after hematopoietic stem cell transplantation present additional risks to ocular health. In conclusion, ocular complications in blood cancer patients are an integral part of patient management, requiring regular ophthalmic evaluations and close collaboration between oncologists and ophthalmologists. Advances in therapy and an increased focus on early symptom recognition are essential for preserving vision and enhancing patient quality of life.
Smoking, Lung Cancer Stage, and Prognostic Factors—Findings from the National Lung Screening Trial
Authors: Zhu Junjia , Branstetter Steven , Lazarus Philip , Muscat Joshua
Published: March 2024

Background: Low-dose computed tomography (LDCT) increases the early detection of lung cancer. Identifying modifiable behaviors that may affect tumor progression in LDCT-detected patients increases the likelihood of long-term survival and a good quality of life. Methods: We examined cigarette smoking behaviors on lung cancer stage, progression, and survival in 299 ever-smoking patients with low-dose CT-detected tumors from the National Lung Screening Trial. Univariate and multivariate Cox models were used to estimate the hazard ratio (HR) for smoking variables on survival time. Results: Current vs. former smokers and early morning smokers (≤5 min after waking, i.e., time to first cigarette (TTFC) ≤ 5 min) had more advanced-stage lung cancer. The adjusted HR for current vs. former smokers was 1.3 (95% confidence interval [CI] 0.911–1.98, p = 0.136) for overall survival (OS) and 1.3 (0.893–1.87, p = 0.1736) for progression-free survival (PFS). The univariate hazard ratios for TTFC ≤ 5 min vs. >5 min were 1.56 (1.1–2.2, p = 0.013) for OS and 1.53 (1.1–2.12, p = 0.01) for PFS. Among current smokers, the corresponding HRs for early TTFC were 1.78 (1.16–2.74, p = 0.0088) and 1.95 (1.29–2.95, p = 0.0016) for OS and PFS, respectively. In causal mediation analysis, the TTFC effect on survival time was mediated entirely through lung cancer stage. Conclusion: The current findings indicate smoking behaviors at diagnosis may affect lung cancer stage and prognosis.
Depression Treatment in Pregnancy: Is It Safe, or Is It Not?
Authors: Gallitelli Vitalba , Franco Rita , Guidi Sofia , Puri Ludovica , Parasiliti Marco , Vidiri Annalisa , Eleftheriou Georgios , Perelli Federica , Cavaliere Anna Franca
Published: March 2024

Prenatal depression carries substantial risks for maternal and fetal health and increases susceptibility to postpartum depression. Untreated depression in pregnancy is correlated with adverse outcomes such as an increased risk of suicidal ideation, miscarriage and neonatal growth problems. Notwithstanding concerns about the use of antidepressants, the available treatment options emphasize the importance of specialized medical supervision during gestation. The purpose of this paper is to conduct a brief literature review on the main antidepressant drugs and their effects on pregnancy, assessing their risks and benefits. The analysis of the literature shows that it is essential that pregnancy be followed by specialized doctors and multidisciplinary teams (obstetricians, psychiatrists and psychologists) who attend to the woman’s needs. Depression can now be treated safely during pregnancy by choosing drugs that have no teratogenic effects and fewer side effects for both mother and child. Comprehensive strategies involving increased awareness, early diagnosis, clear guidelines and effective treatment are essential to mitigate the impact of perinatal depression.
A Settings and Systems Approach to Promoting the Health and Wellbeing of People with an Intellectual Disability
Authors: Joyce Andrew
Published: March 2024

Research has shown that people with an intellectual disability have higher rates of certain preventable health conditions and a higher rate of avoidable mortality relative to the general population. With respect to health behaviours, they also have lower levels of physical activity and poorer nutrition. Despite the increased health needs, this population cohort is less likely to have the opportunity to participate in health promotion programs. The interventions that have been delivered are programmatic and individual in focus and have lacked a broader ecological and settings focus, which makes them very difficult to scale. Health promotion programs designed for the general population, such as lifestyle campaigns, rarely reach people with an intellectual disability. This increases the importance of ensuring that the settings in which they live and engage with are as health promoting as possible. Interventions have been particularly absent in the workplace for people with an intellectual disability. This paper highlights gaps in a settings-and-systems-based approach to promoting the health and wellbeing of people with an intellectual disability, particularly with respect to workplace health promotion. The paper concludes with recommendations for a systems approach that integrates approaches across multiple settings to better promote the health of this population cohort.
How Audit Fees Impact Earnings Management in Service Companies on the Amman Stock Exchange through Audit Committee Characteristics
Authors: Shehadeh Ayman , Nassar Mahmoud Daoud Daoud , Shrouf Husam , Sharairi Mohammad Haroun
Published: March 2024

The primary objective of this research was to investigate the potential moderating role of audit fees in the relationship between audit committee characteristics and earnings management. Specifically, this study aimed to establish connections between audit committee features, such as committee size, member independence, and financial expertise, and the practice of earnings management. To address these research questions, a convenient sample of 46 service providers listed on the Amman Stock Exchange between 2016 and the subsequent year was employed. Descriptive statistical methods were applied to characterize the variables under investigation, while a multiple regression model was utilized to assess the study’s hypotheses. The findings of the study revealed that there was no significant correlation between the size of the audit committee and earnings management. However, a negative correlation was observed between the audit committee’s independence and the financial expertise of its members. Importantly, when audit fees were introduced as a moderating variable, the relationships between committee member independence and earnings management, as well as between committee member financial expertise and earnings management, were found to be weakened. These results have potential implications for policymakers and regulators in Jordan. They may offer valuable insights into corporate governance reforms that could assist Jordanian businesses in enhancing their earnings management practices.
Correction: Zanin et al. Analysis of Radiation Toxicity in Mammalian Cells Stably Transduced with Mitochondrial Stat3. Int. J. Mol. Sci. 2023, 24, 8232
Authors: Zanin Alisa , Meneghetti Giacomo , Menilli Luca , Tesoriere Annachiara , Argenton Francesco , Mognato Maddalena
Published: March 2024

In the original publication [...]
Editorial: Special Issue “Galectins: Structure, Function and Therapeutic Inhibitors”
Authors: Pedone Emilia Maria , Di Gaetano Sonia , Capasso Domenica
Published: March 2024

Galectins, β-galactoside-binding proteins, play relevant roles in different biological processes; therefore, they are becoming emerging targets for diagnostic and therapeutic approaches [...]
Dopamine and Norepinephrine Tissue Levels in the Developing Limbic Brain Are Impacted by the Human CHRNA6 3′-UTR Single-Nucleotide Polymorphism (rs2304297) in Rats
Authors: Carreño Diana , Facundo Antonella , Nguyen My Trang Thi , Lotfipour Shahrdad
Published: March 2024

We previously demonstrated that a genetic single-nucleotide polymorphism (SNP, rs2304297) in the 3′ untranslated region (UTR) of the human CHRNA6 gene has sex- and genotype-dependent effects on nicotine-induced locomotion, anxiety, and nicotine + cue-induced reinstatement in adolescent rats. This study aims to investigate how the CHRNA6 3′-UTR SNP influences dopaminergic and noradrenergic tissue levels in brain reward regions during baseline and after the reinstatement of drug-seeking behavior. Naïve adolescent and adult rats, along with those undergoing nicotine + cue reinstatement and carrying the CHRNA6 3′-UTR SNP, were assessed for dopamine (DA), norepinephrine (NE), and metabolites in reward pathway regions. The results reveal age-, sex-, and genotype-dependent baseline DA, NE, and DA turnover levels. Post-reinstatement, male α6GG rats show suppressed DA levels in the Nucleus Accumbens (NAc) Shell compared to the baseline, while nicotine+ cue-induced reinstatement behavior correlates with neurotransmitter levels in specific brain regions. This study emphasizes the role of CHRNA6 3′-UTR SNP in the developmental maturation of the dopaminergic and noradrenergic system in the adolescent rat brain, with tissue levels acting as predictors of nicotine + cue-induced reinstatement.
Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis
Authors: Soria-Chacartegui Paula , Navares-Gómez Marcos , Molina-Jiménez Francisca , Laserna-Mendieta Emilio J. , Arias-González Laura , Majano Pedro , Casabona Sergio , Lucendo Alfredo J. , Abad-Santos Francisco , Santander Cecilio , Zubiaur Pablo
Published: March 2024

Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (STAT6), CYP2C19, CYP3A4, CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. −75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.
Fibrin Glue Coating Limits Scar Tissue Formation around Peripheral Nerves
Authors: Mayrhofer-Schmid Maximilian , Aman Martin , Panayi Adriana C. , Raasveld Floris V. , Kneser Ulrich , Eberlin Kyle R. , Harhaus Leila , Böcker Arne
Published: March 2024

Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential.
Exogenous Melatonin Application Accelerated the Healing Process of Oriental Melon Grafted onto Squash by Promoting Lignin Accumulation
Authors: Zhu Yulei , Guo Jieying , Wu Fang , Yu Hanqi , Min Jiahuan , Zhao Yingtong , Tan Changhua , Liu Yuanwei , Xu Chuanqiang
Published: March 2024

Melatonin (MT) is a vital hormone factor in plant growth and development, yet its potential to influence the graft union healing process has not been reported. In this study, we examined the effects of MT on the healing of oriental melon scion grafted onto squash rootstock. The studies indicate that the exogenous MT treatment promotes the lignin content of oriental melon and squash stems by increasing the enzyme activities of hydroxycinnamoyl CoA ligase (HCT), hydroxy cinnamaldehyde dehydrogenase (HCALDH), caffeic acid/5-hydroxy-conifer aldehyde O-methyltransferase (COMT), caffeoyl-CoA O-methyltransferase (CCoAOMT), phenylalanine ammonia-lyase (PAL), 4-hydroxycinnamate CoA ligase (4CL), and cinnamyl alcohol dehydrogenase (CAD). Using the oriental melon and squash treated with the exogenous MT to graft, the connection of oriental melon scion and squash rootstock was more efficient and faster due to higher expression of wound-induced dedifferentiation 1 (WIND1), cyclin-dependent kinase (CDKB1;2), target of monopteros 6 (TMO6), and vascular-related NAC-domain 7 (VND7). Further research found that the exogenous MT increased the lignin content of the oriental melon scion stem by regulating CmCAD1 expression, and then accelerated the graft healing process. In addition, the root growth of grafted seedlings treated with the exogenous MT was more vigorous.
Proteomic Analysis of Salivary Extracellular Vesicles from COVID-19 Patients Reveals a Specific Anti-COVID-19 Response Protein Signature
Authors: Weber Laura , Torres Alfredo , Realini Ornella , Bendek María José , Mizgier María Luisa , Brizuela Claudia , Herrera David , González Fermín E. , Chaparro Alejandra
Published: March 2024

Despite the understanding of the coronavirus disease-19 (COVID-19), the role of salivary extracellular vesicles (sEVs) in COVID-19 remains unclear. Exploring the proteomic cargo of sEVs could prove valuable for diagnostic and prognostic purposes in assessing COVID-19. The proteomic cargo of sEVs from COVID-19(+) subjects and their healthy close contacts (HCC) was explored. sEVs were isolated by ultracentrifugation from unstimulated saliva samples, and subsequently characterized through nanoparticle tracking, transmission electron microscopy, and Western blot analyses. The proteomic cargo of sEVs was processed by LC-MS/MS. sEVs were morphologically compatible with EVs, with the presence of Syntenin-1 and CD81 EV markers. The sEV pellet showed 1417 proteins: 1288 in COVID-19(+) cases and 1382 in HCC. In total, 124 proteins were differentially expressed in sEVs from COVID-19(+) subjects. “Coronavirus-disease response”, “complement and coagulation cascades”, and “PMN extracellular trap formation” were the most enriched KEGG pathways in COVID-19(+) cases. The most represented biological processes were “Hemoglobin and haptoglobin binding” and “oxygen carrier activity”, and the best-denoted molecular functions were “regulated exocytosis and secretion” and “leucocyte and PMN mediated immunity”. sEV proteomic cargo in COVID-19(+) suggests activity related to immune response processes, oxygen transport, and antioxidant mechanisms. In contrast, in HCC, sEV signature profiles are mainly associated with epithelial homeostasis.
Retention Rates of Genetic Therapies Based on AAV Serotypes 2 and 8 Using Different Drug-Delivery Materials
Authors: Reichel Felix F. , Kiraly Peter , Seitz Immanuel P. , Fischer M. Dominik
Published: March 2024

The purpose of this study was to compare the retention rate of Adeno-associated viral vector (AAV) gene therapy agents within different subretinal injection systems. The retention of AAV serotype 2-based voretigene neparvovec (VN) and a clinical-grade AAV serotype 8 vector within four different subretinal cannulas from two different manufacturers was quantified. A standardized qPCR using the universal inverted terminal repeats as a target sequence was developed. The instruments compared were the PolyTip® cannula 25 g/38 g by MedOne Surgical, Inc., Sarasota, FL, USA, and three different subretinal injection needles by DORC, Zuidland, The Netherlands (1270.EXT Extendible 41G subretinal injection needle (23G), DORC 1270.06 23G Dual bore injection cannula, DORC 27G Subretinal injection cannula). The retention rate of VN and within the DORC products (10–28%) was comparable to the retention rate (32%) found for the PolyTip® cannula that is mentioned in the FDA-approved prescribing information for VN. For the AAV8 vector, the PolyTip® cannula showed a retention rate of 14%, and a similar retention rate of 3–16% was found for the DORC products (test–retest variability: mean 4.5%, range 2.5–20.2%). As all the instruments tested showed comparable retention rates, they seem to be equally compatible with AAV2- and AAV8-based gene therapy agents.
Gene Silencing of Angiopoietin-like 3 (ANGPTL3) Induced De Novo Lipogenesis and Lipid Accumulation in Huh7 Cell Line
Authors: Rossi Ilaria , Marodin Giorgia , Lupo Maria Giovanna , Adorni Maria Pia , Papotti Bianca , Dall’Acqua Stefano , Ferri Nicola
Published: March 2024

Angiopoietin-like 3 (ANGPTL3) is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL). Vupanorsen, an ANGPTL3 directed antisense oligonucleotide, showed an unexpected increase in liver fat content in humans. Here, we investigated the molecular mechanism linking ANGPTL3 silencing to hepatocyte fat accumulation. Human hepatocarcinoma Huh7 cells were treated with small interfering RNA (siRNA) directed to ANGPTL3, human recombinant ANGPTL3 (recANGPTL3), or their combination. Using Western blot, Oil Red-O, biochemical assays, and ELISA, we analyzed the expression of genes and proteins involved in lipid metabolism. Oil Red-O staining demonstrated that lipid content increased after 48 h of ANGPTL3 silencing (5.89 ± 0.33 fold), incubation with recANGPTL3 (4.08 ± 0.35 fold), or their combination (8.56 ± 0.18 fold), compared to untreated cells. This effect was also confirmed in Huh7-LX2 spheroids. A total of 48 h of ANGPTL3 silencing induced the expression of genes involved in the de novo lipogenesis, such as fatty acid synthase, stearoyl-CoA desaturase, ATP citrate lyase, and Acetyl-Coenzyme A Carboxylase 1 together with the proprotein convertase subtilisin/kexin 9 (PCSK9). Time-course experiments revealed that 6 h post transfection with ANGPTL3-siRNA, the cholesterol esterification by Acyl-coenzyme A cholesterol acyltransferase (ACAT) was reduced, as well as total cholesterol content, while an opposite effect was observed at 48 h. Under the same experimental conditions, no differences in secreted apoB and PCSK9 were observed. Since PCSK9 was altered by the treatment, we tested a possible co-regulation between the two genes. The effect of ANGPTL3-siRNA on the expression of genes involved in the de novo lipogenesis was not counteracted by gene silencing of PCSK9. In conclusion, our in vitro study suggests that ANGPTL3 silencing determines lipid accumulation in Huh7 cells by inducing the de novo lipogenesis independently from PCSK9.
Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability
Authors: Hudhud Lina , Rozmer Katalin , Kecskés Angéla , Pohóczky Krisztina , Bencze Noémi , Buzás Krisztina , Szőke Éva , Helyes Zsuzsanna
Published: March 2024

Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive 45Ca2+ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant 45Ca2+ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate 45Ca2+ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC50 values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives.
Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research
Authors: Farh Mohamed El-Agamy , Kim Hyun-Jin , Kim Sang-Yeon , Lee Jae-Hee , Lee Hajeong , Cui Ronglan , Han Soorim , Kim Dong Wook , Park Sunjoo , Lee Yoon-Jin , Lee Yun-Sil , Sohn Insuk , Cho Jaeho
Published: March 2024

In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.
Dynamic Changes of the Gut Microbiota and Its Functional Metagenomic Potential during the Development of Non-Small Cell Lung Cancer
Authors: Feng Cuijiao , Li Na , Gao Guangqi , He Qiuwen , Kwok Lai-Yu , Zhang Heping
Published: March 2024

The gut microbiota plays a significant role in tumor pathogenesis by regulating the host metabolism and immune response, and there are few studies focused on tracking changes in the gut microbiota from the onset of lung cancer. Therefore, the aim of our study is combining preclinical and clinical research to thoroughly analyze the signatures of fecal microbiota in lung cancer, which will be useful for early diagnosis and predicting the therapeutic efficacy of lung cancer. The first part of this study analyzed the fecal metagenomic differences between patients with non-small cell lung cancer and healthy subjects, and the second part of this work constructed a murine lung cancer model to monitor changes in mouse fecal metagenomics and T cell immunology during lung cancer progression. We found that the fecal microbiota was altered in both humans and mice with lung cancer, characterized by a significantly reduced microbial diversity and number of beneficial microbes, with increases in potential pathogens. The fecal level of Akkermansia muciniphila and the gut metabolic module of the secondary bile acid metabolism were diminished in both humans and mice with lung cancer compared with healthy subjects. Splenomegaly was observed in the lung cancer mice. Flow cytometer analysis of the splenocytes revealed substantial alterations in the proportions of T cell subsets in the lung cancer mice, characterized by significant increases in CD4+Foxp3+CD25+ T regulatory cells (p < 0.05) while significant decreases in CD3+ T cells (p < 0.001), CD4+ T cells (p < 0.001), and the CD4+/CD8+ ratio (p < 0.01). Vertical and longitudinal analyses of the fecal microbiota of the two mouse groups identified some lung cancer biomarkers (including Acutalibacter timonensis, Lachnospiraceae bacterium NSJ-38 sp014337195, etc.). The fecal microbiota of the lung cancer mice had a reduced metagenomic potential for neurotransmitters (melatonin, γ-aminobutyric acid, and histamine) compared with healthy mice. In summary, this study found that the diversity, structure, and composition of gut microbiota vary between cancer and healthy conditions, ultimately leading to changes in the potential for functional metagenomics.