bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Soil Health and Tea Plant Quality Through Integrated Organic and Chemical Fertilization Strategies
Authors: Miao Pengyao , Pang Xiaomin , Zhang Mengzhen , Cheng Weiting , Zhou Zewei , Li Yuanping , Wang Haibin , Jia Xiaoli , Ye Jianghua , Zhang Qi
Published: December 2024

As the global demand for high-quality tea increases, adopting sustainable agricultural practices is crucial to maintaining environmental health and improving crop productivity. Employing organic fertilizers has the potential to boost agricultural output and improve soil health, as well as curb the spread of pests and diseases. The purpose of this survey was to determine the impact of a range of organic fertilizer mixtures on both tea plants and rhizosphere soil characteristics in tea plantations. This study investigated the response of Jin Guanyin tea (Camellia sinensis L.) plants to various organic fertilizer ratios: 2/3 chemical fertilizer + 1/3 organic fertilizer (JTC), 1/2 chemical fertilizer + 1/2 organic fertilizer (JHOC), 1/3 chemical fertilizer + 2/3 organic fertilizer (JTO), and organic fertilizer only (JOF), with chemical fertilizer alone (JCF) as the control. The experiment was conducted in Xingcun Town, Wuyishan, Fujian Province, China, on 13 October 2021. Key metrics measured included tea plant growth indicators, soil physicochemical properties, enzyme activities, and microbial functional diversity. Results show that JTC and JTO produce the largest leaf area and bud weight, significantly surpassing those in JCF. JCF demonstrated the longest new tip length and highest bud density, while JHOC achieved the highest chlorophyll content, significantly exceeding JCF. Soil analysis revealed that total nitrogen, available nitrogen, organic matter, and pH were highest in JOF, significantly overtaking JCF. Conversely, total phosphorus, available potassium, and available phosphorus levels were highest in JCF. JHOC also had the highest total potassium content compared to JCF. Soil enzyme activity assessments showed that polyphenol oxidase and urease activities peaked in JTC, significantly exceeding those in JCF. JHOC exhibited the highest acid phosphatase activity, while JTO exhibited the highest protease activity. Catalase activity was highest in JOF, both significantly surpassing JCF. Microbial functional diversity analysis indicated that combined organic fertilization improved soil microorganisms’ utilization of carbon sources, significantly enhancing the Shannon diversity index and evenness. Key carbon sources identified included α-cyclodextrin, D-galacturonic acid, and 4-hydroxy benzoic acid. Overall, JHOC emerged as the optimal fertilization strategy, yielding superior growth indicators, enhanced soil physicochemical properties, increased enzyme activity, and improved microbial functional diversity compared to JCF. This study has important value for guiding the rational application of fertilizers in tea gardens, improving the soil environment of tea gardens, enhancing the quality of tea leaves, and achieving sustainable tea production.
Characterizing Soil and Bedrock Water Use of Native California Vegetation
Authors: Flint Alan L. , Flint Lorraine E. , Stern Michelle A. , Ackerly David D. , Boynton Ryan , Thorne James H.
Published: December 2024

The effective characterization of landscape water balance components—evapotranspiration, runoff, recharge, and soil storage—is critical for understanding the integrated effects of the water balance on vegetation dynamics, water availability, and associated environmental responses to climate change. An improved parameterization of these components can improve assessments of landscape stress and provide useful insights for predicting and managing vegetation responses to climate change. Hydrology models typically are not able to address water availability below the mapped soil profile, but we refined a landscape hydrology model, the Basin Characterization Model, by balancing measures of actual evapotranspiration (AET) with modeled subsurface soil water holding capacity, including bedrock storage. The purpose of this study was to characterize the effective rooting depth (the depth of soil and bedrock storage required to support AET) for 35 native vegetation types in California in order to quantify soil and bedrock water use, which ranged from 0 to 3.1 m for most vegetation types, exceeding mapped soil depths. This resulted in the quantification of bedrock water use, increasing available water 67% over that calculated by mapped soils alone. We found that mid-elevation vegetation types with lower water and energy limitations have the highest evapotranspiration rates and deepest effective rooting depth. We also evaluated the resilience to drought with this more spatially realistic characterization of water and vegetation interactions.
Entity-Driven New Paradigm of Mine Data: Model Construction and Application
Authors: Li Wenjing , Ma Qian , Tang Yanbin , Lin Zhiyong
Published: December 2024

In the construction of a three-dimensional real scene (3D real scene) of a mine, we encounter challenges in organizing and correlating multi-source data. To surmount these challenges, we innovatively adopted the entity organization method. We proposed a definition of a “mining entity” and conducted an in-depth analysis of its main characteristics. Based on these characteristics, we classified and coded the main mining entities and further constructed an entity expression pattern layer that could fully reflect the characteristics of the mine. Based on multi-source heterogeneous mine data, we constructed a mining entity data layer. Furthermore, by adopting a graph database approach, we were able to create a graphical representation and correlation application of the complex relationships among mining entities. This work shows that compared to traditional data management methods, a mine data organization approach centered on entities can more effectively integrate and correlate multi-source mine data, providing strong support for the digital management of mines and the construction of 3D real scenes.
Spatial Pattern and Influencing Factors of Tourist Attractions in Coastal Cities: A Case Study of Qingdao
Authors: Xu Yue , Zhang Xuliang , Zhang Kuncheng , Yu Jing , Liu Jia
Published: December 2024

The spatial distribution of tourist attractions plays a critical role in the development of coastal cities. Qingdao, with its coastal geography, rich cultural heritage, and rapid urbanization, serves as a representative case. This study integrates POI and multi-source data, employing methods such as the average nearest neighbor index, kernel density estimation, standard deviational ellipse, and Geodetector to analyze the spatial characteristics and influencing factors of Qingdao’s tourist attractions. Additionally, path dependence theory is innovatively applied to elucidate the mechanisms of the city’s development trajectory. Both natural and social factors influence this distribution, where the resource environment forms the foundational basis, the economic development provides impetus, and the urban development orientation exerts a regulatory effect. The findings are broadly applicable to other coastal tourist cities and offer strategic insights for sustainable development in such contexts.
Effect of Natalizumab on sNfL and sGFAP Levels in Multiple Sclerosis Patients
Authors: Sainz-Amo Raquel , Rodero-Romero Alexander , Monreal Enric , Chico-García Juan Luis , Rodríguez-Jorge Fernando , Fernández-Velasco Jose Ignacio , Villarrubia Noelia , Veiga-González Jose Luis , de la Maza Susana Sainz , Masjuan Jaime , Costa-Frossard Lucienne , Villar Luisa Maria
Published: December 2024

Natalizumab is a highly effective therapy for multiple sclerosis (MS). The aim of this study was to evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing–remitting MS treated with Natalizumab. sNfL and sGFAP were analyzed at baseline, 6 and 12 months post treatment using the single-molecule array (SiMoA) technique. We recruited matched healthy controls for comparison. The study included 54 patients, with a median age of 33 years (Interquartile range (IQR), 29–41), with 32 women (60%) and 76 healthy controls. A decrease in sNfL was observed at 6 (67%, p = 0.005) and 12 (72%, p < 0.0001) months compared to baseline. After two years, six patients experienced evidence of disease activity (EDA-3). The remaining ones had no evidence of disease activity (NEDA-3). NEDA-3 presented a remarkable reduction in sNfL (p < 0.0001) and sGFAP (p = 0.01) after 6 months of treatment that continued to be observed after 12 months compared to baseline. EDA-3 only reached a significant decrease in sNfL after 12 months; there were no significant changes in sGFAP values. Natalizumab leads to a decrease in sNfL, which is higher and occurs earlier in NEDA-3 patients. Patients also showed a significant reduction in sGFAP levels, which was not observed in the EDA-3 group.
The Role of Hypothalamic Microglia in the Onset of Insulin Resistance and Type 2 Diabetes: A Neuro-Immune Perspective
Authors: Darwish Radwan , Alcibahy Yasmine , Bucheeri Shahd , Albishtawi Ashraf , Tama Maya , Shetty Jeevan , Butler Alexandra E.
Published: December 2024

Historically, microglial activation has been associated with diseases of a neurodegenerative and neuroinflammatory nature. Some, like Alzheimer’s disease, Parkinson’s disease, and multiple system atrophy, have been explored extensively, while others pertaining to metabolism not so much. However, emerging evidence points to hypothalamic inflammation mediated by microglia as a driver of metabolic dysregulations, particularly insulin resistance and type 2 diabetes mellitus. Here, we explore this connection further and examine pathways that underlie this relationship, including the IKKβ/NF-κβ, IRS-1/PI3K/Akt, mTOR-S6 Kinase, JAK/STAT, and PPAR-γ signaling pathways. We also investigate the role of non-coding RNAs, namely microRNAs and long non-coding RNAs, in insulin resistance related to neuroinflammation and their diagnostic and therapeutic potential. Finally, we explore therapeutics further, searching for both pharmacological and non-pharmacological interventions that can help mitigate microglial activation.
Salt-Controlled Vertical Segregation of Mixed Polymer Brushes
Authors: Mikhailov Ivan V. , Darinskii Anatoly A.
Published: December 2024

Using the self-consistent field approach, we studied the salt-controlled vertical segregation of mixed polymer brushes immersed into a selective solvent. We considered brushes containing two types of chains: polyelectrolyte (charged) chains and neutral chains. The hydrophobicity of both types of chains is characterized by the Flory–Huggins parameters χC and χN, respectively. It was assumed that the hydrophobicity is varied only for the polyelectrolyte chains (χC), while other polymer chains in the brush remain hydrophilic (χN=0) and neutral. Thus, in our model, the solvent selectivity (χ=χC−χN) was varied, which can be controlled in a real experiment, for example, by changing the temperature. At low salt concentrations, the polyelectrolyte chains swell and occupy the surface of the mixed brush. At high salt concentrations, the hydrophobic polyelectrolyte chains collapse and give place to neutral chains on the surface. By changing the selectivity of the solvent and the ionic strength of the solution, the surface properties of such mixed brushes can be controlled. Based on the numerical simulations results, it is shown how the critical selectivity corresponding to the segregation transition in polyelectrolyte/neutral brushes depends on the ionic strength of the solution. It is shown that at the same ionic strength, the critical selectivity increases with an increasing degree of dissociation of charged groups, as well as with an increasing fraction of polyelectrolyte chains in the mixed brush. It has also been shown that at low ionic strengths, the critical selectivity of the solvent decreases with increasing grafting density, while at high ionic strengths, on the contrary, it increases. Within the framework of the mean field theory, a two-parameter model has been constructed that quantitatively describes these dependencies.
Secondary Brain Injury After Parenchymal Cerebral Hemorrhage in Humans: The Role of NOX2-Mediated Oxidative Stress and Endothelin-1
Authors: De Michele Manuela , Amisano Paolo , Schiavo Oscar G. , Cammisotto Vittoria , Carnevale Roberto , Forte Maurizio , Picchio Vittorio , Ciacciarelli Antonio , Berto Irene , Angeloni Ugo , Pugliese Silvia , Toni Danilo , Lorenzano Svetlana
Published: December 2024

Perihematomal hypoperfusion may lead to ischemic damage during intraparenchymal cerebral hemorrhage (ICH), resulting in worse prognosis. We aimed to (1) investigate the relationship between serum biomarkers related to oxidative stress and vasoactive substances and the occurrence of hypoperfusion and ischemic perihematomal lesions in ICH and (2) evaluate their correlation with the volumetric evolution of the hematoma and perihematomal edema. We enrolled 28 patients affected by ICH. Blood samples were collected at three different time points from symptom onset: T0, T1, and T2 (admission, 12–24 h, and 48–72 h, respectively), to measure endothelin-1 (ET-1), nitrites/nitrates (NO), soluble nicotinamide adenine dinucleotide 2 (NOX2)-derived peptide (sNOX2-dp), and asymmetric dimethylarginine (ADMA). Patients underwent brain MRI with perfusion study at T1 and MRI without perfusion at T2. 12 patients had ischemic perihematomal lesions at T1. A higher sNOX2-dp concentration at T0 was observed in patients with ischemic perihematomal lesions compared to those without (p = 0.051) and with a more severe perihematomal edema at T2 (p = 0.011). The ischemic perihematomal lesions development was also associated with an increased hematoma volume (p < 0.005), perilesional edema (p = 0.046), and greater midline shift (p = 0.036). ET-1 values at T1 were inversely correlated with hemorrhage volume at T2 (ρ = −0.717, p = 0.030). NOX2 activation may have a role in the development of ischemic perihematomal lesions. The association between higher ET-1 values and a lower hemorrhage volume could be related to the ET-1 vasoconstriction action on the ruptured vessel wall.
Multiple Tumors in a Patient with Interleukin-2-Inducible T-Cell Kinase Deficiency: A Case Report
Authors: Di Filippo Michela , Tallone Ramona , Muraca Monica , Pelanconi Lisa , Faravelli Francesca , Capra Valeria , De Marco Patrizia , Ognibene Marzia , Baldassari Simona , Terranova Paola , Livellara Virginia , Vellone Valerio Gaetano , Miano Maurizio , Amoroso Loredana , Beccaria Andrea
Published: December 2024

Immune dysregulation in Inborn Errors of Immunity (IEI) shows a broad phenotype, including autoimmune disorders, benign lymphoproliferation, and malignancies, driven by an increasing number of implicated genes. Recent findings suggest that childhood cancer survivors (CCSs) may exhibit immunological abnormalities potentially linked to an underlying IEI, along with a well-known increased risk of subsequent malignancies due to prior cancer treatments. We describe a patient with two composite heterozygous pathogenic variants in the interleukin-2-inducible T-cell kinase (ITK) gene and a history of multiple tumors, including recurrent Epstein–Barr virus (EBV)-related nodular sclerosis and Hodgkin’s lymphoma (NSHL), associated with unresponsive multiple hand warts, immune thrombocytopenia, and an impaired immunological profile (CD4+ lymphocytopenia, memory B-cell deficiency, reduction in regulatory T-cells, and B-cell- and T-cell-activated profiles). In our case, ITK-related immune dysregulation and prior exposure to oncological treatments seem to have simultaneously intervened in the same individual, leading to the development of a unique clinical profile. It is essential to raise awareness of the two-way association between immune dysregulation disorders and multiple tumors.
Intricate Structure–Function Relationships: The Case of the HtrA Family Proteins from Gram-Negative Bacteria
Authors: Zarzecka Urszula , Skorko-Glonek Joanna
Published: December 2024

Proteolytic enzymes play key roles in living organisms. Because of their potentially destructive action of degrading other proteins, their activity must be very tightly controlled. The evolutionarily conserved proteins of the HtrA family are an excellent example illustrating strategies for regulating enzymatic activity, enabling protease activation in response to an appropriate signal, and protecting against uncontrolled proteolysis. Because HtrA homologs play key roles in the virulence of many Gram-negative bacterial pathogens, they are subject to intense investigation as potential therapeutic targets. Model HtrA proteins from bacterium Escherichia coli are allosteric proteins with reasonably well-studied properties. Binding of appropriate ligands induces very large structural changes in these enzymes, including changes in the organization of the oligomer, which leads to the acquisition of the active conformation. Properly coordinated events occurring during the process of HtrA activation ensure proper functioning of HtrA and, consequently, ensure fitness of bacteria. The aim of this review is to present the current state of knowledge on the structure and function of the exemplary HtrA family proteins from Gram-negative bacteria, including human pathogens. Special emphasis is paid to strategies for regulating the activity of these enzymes.
The Complex Connection Between Myocardial Dysfunction and Cancer Beyond Cardiotoxicity: Shared Risk Factors and Common Molecular Pathways
Authors: Molnár Andrea Ágnes , Birgés Kristóf , Surman Adrienn , Merkely Béla
Published: December 2024

Cardiovascular diseases and cancer represent the largest disease burden worldwide. Previously, these two conditions were considered independent, except in terms of cardiotoxicity, which links cancer treatment to subsequent cardiovascular issues. However, recent studies suggest that there are further connections between cancer and heart disease beyond cardiotoxicity. It has been revealed that myocardial dysfunction may promote carcinogenesis, indicating that additional common pathophysiological mechanisms might be involved in the relationship between cardiology and oncology, rather than simply a connection through cardiotoxic effects. These mechanisms may include shared risk factors and common molecular pathways, such as persistent inflammation and neurohormonal activation. This review explores the connection between myocardial dysfunction and cancer, emphasizing their shared risk factors, similar biological mechanisms, and causative factors like cardiotoxicity, along with their clinical implications.
Wheat WW Domain-Containing Protein TaCFL1 Negatively Regulates Cuticular Wax Biosynthesis
Authors: Chen Wanzhen , Liu Lang , Wang Xiaoyu , Li Haoyu , Liu Jiao , Zhi Pengfei , Chang Cheng
Published: December 2024

Waxy cuticle covers plant aerial organs and protects plants against environmental challenges. Although improved cuticle-associated traits are aimed at the wheat breeding programs, the mechanism governing wheat cuticular wax biosynthesis remains to be elucidated. Herein, wheat WW domain-containing protein TaCFL1 is characterized as a negative regulator of wax biosynthesis. The knockdown of TaCFL1 expression results in a 15% increase in wax accumulation and decreased leaf cuticle permeability in bread wheat. Furthermore, wheat class IV homeodomain transcription factors TaHDG1.1 and TaHDG1.2 are identified as partially redundant activators of wax biosynthesis. The silencing of TaHDG1.1 or TaHDG1.2 expression leads to an 11% reduction in epidermal wax accumulation and an increase in leaf cuticle permeability wax, while the co-silencing of TaHDG1.1 and TaHDG1.2 results in a 31% reduction in epidermal wax accumulation and a further increase in wax in the leaf cuticle permeability. Moreover, wheat 3-Ketoacyl-CoA synthase TaKCS10 is isolated as an essential component of the wax biosynthetic machinery. The silencing of TaKCS10 expression results in a 22% reduction in wax accumulation and increased leaf cuticle permeability. In addition, we demonstrated that the TaKCS10 expression is activated by TaHDG1.1 and TaHDG1.2, and that TaCFL1 attenuates the TaHDG1-mediated transcriptional activation of TaKCS10. This evidence supports that the WW domain-containing protein TaCFL1 negatively regulates wax biosynthesis via attenuating the transcriptional activation of the TaKCS10 gene mediated by HD-ZIP IV transcription factor TaHDG1.
Emerging Biomarkers in Metabolomics: Advancements in Precision Health and Disease Diagnosis
Authors: Vo Dang-Khoa , Trinh Kieu The Loan
Published: December 2024

Metabolomics has come to the fore as an efficient tool in the search for biomarkers that are critical for precision health approaches and improved diagnostics. This review will outline recent advances in biomarker discovery based on metabolomics, focusing on metabolomics biomarkers reported in cancer, neurodegenerative disorders, cardiovascular diseases, and metabolic health. In cancer, metabolomics provides evidence for unique oncometabolites that are important for early disease detection and monitoring of treatment responses. Metabolite profiling for conditions such as neurodegenerative and mental health disorders can offer early diagnosis and mechanisms into the disease especially in Alzheimer’s and Parkinson’s diseases. In addition to these, lipid biomarkers and other metabolites relating to cardiovascular and metabolic disorders are promising for patient stratification and personalized treatment. The gut microbiome and environmental exposure also feature among the influential factors in biomarker discovery because they sculpt individual metabolic profiles, impacting overall health. Further, we discuss technological advances in metabolomics, current clinical applications, and the challenges faced by metabolomics biomarker validation toward precision medicine. Finally, this review discusses future opportunities regarding the integration of metabolomics into routine healthcare to enable preventive and personalized approaches.
Effect of Meropenem on Conjugative Plasmid Transfer in Klebsiella pneumoniae
Authors: Kondratieva Daria A. , Savelieva Julia R. , Golikova Maria V.
Published: December 2024

Plasmid-mediated resistance is a major mechanism that contributes to the gradual decline in the effectiveness of antibiotics from different classes, including carbapenems. Antibiotics can significantly contribute to the efficiency of plasmid transfer between bacterial strains. To investigate the potential effect of an antibiotic on the efficacy of conjugative plasmid transfer, we conducted mating experiments with Klebsiella pneumoniae strains. Donor strains of K. pneumoniae that carry plasmids with blaKPC or blaOXA-48 carbapenemase genes and recipient plasmid-free K. pneumoniae strains were used in matings. Matings were conducted on the agar with or without meropenem at 1/8×, 1/4×, or 1/2×MIC against the respective recipients. In the second part of our study, we investigated the pharmacodynamic properties of meropenem against transconjugant strains of K. pneumoniae, which were obtained in the first part of this study. As a result, at a concentration equivalent to 1/8×MIC, meropenem primarily inhibited conjugation among K. pneumoniae strains, while at a concentration equal to 1/2×MIC, it facilitated conjugation. Transconjugants derived from K. pneumoniae with intermediate MICs failed to respond to simulated treatment with meropenem using prolonged infusion and a high-dose regimen. This finding suggests that such transconjugants may potentially pose a risk if involved in an infectious process.
Feline Diabetes Is Associated with Deficits in Markers of Insulin Signaling in Peripheral Tissues
Authors: Patra Souvik , McMillan Chantal J. , Snead Elisabeth R. , Warren Amy L. , Cosford Kevin , Chelikani Prasanth K.
Published: December 2024

Like humans, cats have a strong relationship between decreasing insulin sensitivity and the development of diabetes with obesity. However, the underlying molecular mechanisms of impaired insulin secretion and signaling in cats remain largely unknown. A total of 54 client-owned nondiabetic lean (n = 15), overweight (n = 15), and diabetic (n = 24) cats were included in the study. The pancreas, liver, and skeletal muscle were quantified for mRNA and protein abundances of insulin and incretin signaling markers. Diabetic cats showed increased liver and muscle adiposity. The pancreas of diabetic cats had decreased transcript abundances of insulin, insulin receptor, insulin-receptor substrate (IRS)-1, glucose transporters (GLUT), and protein abundance of mitogen-activated protein kinase. In treated diabetics, protein abundance of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide receptors, total and phosphorylated Akt, and GLUT-1 were increased in the pancreas, whereas untreated diabetics had downregulation of markers of insulin and incretin signaling. In the muscle and liver, diabetic cats had reduced mRNA abundances of insulin receptor, IRS-1/2, and phosphatidylinositol-3-kinase, and reduced protein abundances of GLUT-4 and phosphatidylinositol-3-kinase-p85α in muscle. We demonstrate that feline diabetes is associated with ectopic lipid deposition in the liver and skeletal muscle, deficits in insulin synthesis and incretin signaling in the pancreas, and impaired insulin signaling in the muscle and liver. These findings have implications for understanding the pathophysiological mechanisms of obesity and diabetes in humans and pets.
Dopamine: A New Player in the Pathogenesis of Diabetic Retinopathy?
Authors: Ntikoudi Marianthi , Farmaki Theofano Myrto , Tziomalos Konstantinos
Published: December 2024

Diabetic retinopathy (DR) is a leading cause of blindness. The pathogenesis of diabetic retinopathy is multifactorial and incompletely understood. Accordingly, treatment options are limited. Recent data suggest that dopamine might play a role in the development and progression of DR. In the present review, we discuss these data and comment on the potential role of dopamine modulation in the management of this devastating microvascular complication of diabetes mellitus.
Sex-Specific HLA Alleles Contribute to the Modulation of COVID-19 Severity
Authors: Spartano Serena , Faggiano Maria Vittoria , Guidi Giovanna , D’Ambrosio Pino , Vaisfeld Alessandro , Novelli Agnese , Falqui Salvatore , Cingolani Antonella , Lambertenghi Lorenza , Visentin Alessandro , Azzini Annamaria , Righi Elda , Trecarichi Enrico Maria , Mazzitelli Maria , Coletti Silvano , Mous Jan , Rademacher Thomas W. , Torti Carlo , Tacconelli Evelina , Fantoni Massimo , Cauda Roberto , Tiziano Francesco Danilo
Published: December 2024

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, responsible for Coronavirus Disease 2019 (COVID-19), exhibits a spectrum of clinical manifestations, ranging from asymptomatic to severe pulmonary dysfunction or death. The variability in COVID-19 severity has largely been attributed to the host’s genetic characteristics, suggesting a polygenic genetic architecture, without significant strong evidence of sex-related genetic differences. In this Italian retrospective case–control study, we investigated the association between COVID-19 severity (severe vs. asymptomatic/oligosymptomatic healed individuals) and HLA gene variants, analyzed by next-generation sequencing (NGS). We identified significant HLA alleles (according to the conventional nomenclature), SNPs and haplotypes in the HLA-B, -C, -F, -DQA1, -DRB1, and -DRB5 genes associated with COVID-19 severity. Interestingly, these variants showed biological sex-related effects. Also, we identified specific haplotypes associated with COVID-19 severity that are shared by different conventional HLA alleles, indicated here as “super-haplotypes”. These haplotypes had a biological sex-specific impact on disease severity and markedly increased the risk of severe COVID-19 compared to the conventional HLA alleles (odds ratio of up to 15). Our data suggest that the revision of the current HLA nomenclature may help to identify variants with a stronger effect on disease susceptibility and that association studies could benefit from the stratification of patients by biological sex. If replicated in other disease models, these findings could help to define the functional diversity in immune response between sexes, also based on the HLA system. Finally, due to the global pandemic’s mortality rate, we hypothesize here that SARS-CoV-2 may have acted as a natural selection trigger, leading to a drift in HLA allelic frequencies in the general population.
Development of a Multiplex RT–qPCR Method for the Identification and Lineage Typing of Porcine Reproductive and Respiratory Syndrome Virus
Authors: Tao Chunhao , Zhu Xizhou , Huang Ying , Yuan Weifeng , Wang Zhen , Zhu Hongfei , Jia Hong
Published: December 2024

Porcine reproductive and respiratory syndrome virus (PRRSV) is the pathogen that causes porcine reproductive and respiratory syndrome (PRRS), leading to abortion of sows and the manifestation of respiratory diseases in piglets. PRRSV strains are categorized into two distinct genotypes: PRRSV–1 and PRRSV–2. PRRSV–2 can be further classified into several lineages, including sub–lineage 1.8 (NADC30–like), sub–lineage 1.5 (NADC34–like), lineage 8 (HP–PRRSV–like), lineage 5 (VR–2332–like), and lineage 3 (QYYZ–like), all of which are prevalent in China. In order to identify PRRSV–1 and PRRSV–2, two primer–probe combinations were designed, targeting the M gene. In order to further differentiate the five lineages of PRRSV–2, another five primer–probe combinations were designed, targeting the Nsp2 gene. A TaqMan–based multiplex RT–qPCR assay was subsequently developed, integrating the aforementioned seven sets into two primer pools. Following the optimization of primer concentration and annealing temperature, a comprehensive evaluation was conducted to assess the assay’s amplification efficiency, specificity, repeatability, and sensitivity. The developed multiplex RT–qPCR method exhibited excellent repeatability, with coefficients of variation (CVs) less than 2.12%. The detection limits for all seven targets were found to be less than 5 copies/μL. Ultimately, the method was utilized for the detection of a total of 1009 clinical samples, with a PRRSV–positive rate of 7.63% (77/1009). Specifically, the reference method was utilized to further confirm the status of the 77 PRRSV–positive samples and another 27 samples suspected of PRRSV infection. The sensitivity of the method was 97.40% (75/77), and the specificity was 96.30% (26/27), resulting in an overall coincidence rate of 97.12% (101/104). All the PRRSV–positive samples were typed as NADC30–like strains, and the accuracy of this typing was further confirmed by Sanger sequencing. In conclusion, A one–step multiplex RT–qPCR method was successfully constructed, evaluated, and applied to detect clinical samples. The assay provides an easy–to–operate, time–saving, and highly efficient way for the quick identification of PRRSV and simultaneous detection of five PRRSV–2 lineages prevalent in China. The method could offer guidance for PRRSV prevention and control measures.
Diacylglycerol Kinases and Its Role in Lipid Metabolism and Related Diseases
Authors: Liu Yishi , Yang Zehui , Zhou Xiaoman , Li Zijie , Hideki Nakanishi
Published: December 2024

Lipids are essential components of eukaryotic membranes, playing crucial roles in membrane structure, energy storage, and signaling. They are predominantly synthesized in the endoplasmic reticulum (ER) and subsequently transported to other organelles. Diacylglycerol kinases (DGKs) are a conserved enzyme family that phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), both of which are key intermediates in lipid metabolism and second messengers involved in numerous cellular processes. Dysregulation of DGK activity is associated with several diseases, including cancer and metabolic disorders. In this review, we provide a comprehensive overview of DGK types, functions, cellular localization, and their potential as therapeutic targets. We also discuss DGKs’ roles in lipid metabolism and their physiological functions and related diseases.
A Diagnostic Approach in Large B-Cell Lymphomas According to the Fifth World Health Organization and International Consensus Classifications and a Practical Algorithm in Routine Practice
Authors: Zanelli Magda , Sanguedolce Francesca , Zizzo Maurizio , Ricci Stefano , Bisagni Alessandra , Palicelli Andrea , Fragliasso Valentina , Donati Benedetta , Broggi Giuseppe , Boutas Ioannis , Koufopoulos Nektarios , Foroni Moira , Coppa Francesca , Morini Andrea , Parente Paola , Zuccalà Valeria , Caltabiano Rosario , Fabozzi Massimiliano , Cimino Luca , Neri Antonino , Ascani Stefano
Published: December 2024

In this article, we provide a review of large B-cell lymphomas (LBCLs), comparing the recently published fifth edition of the WHO classification and the International Consensus Classification (ICC) on hematolymphoid tumors. We focus on updates in the classification of LBCL, an heterogeneous group of malignancies with varying clinical behaviors and different pathological and molecular features, providing a comparison between the two classifications. Besides the well-recognized diagnostic role of clinical, morphological and immunohistochemical data, both classifications recognize the ever-growing impact of molecular data in the diagnostic work-up of some entities. The main aim is to offer a guide for clinicians and pathologists on how the new classifications can be applied to LBCL diagnosis in routine practice. In the first part of the paper, we review the following categories: LBLs transformed from indolent B-cell lymphomas, diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), double-hit/triple-hit lymphomas (DH/TH), high-grade large B-cell lymphoma, not otherwise specified (HGBCL, NOS), LBCL with IRF4 rearrangement, Burkitt lymphoma (BL) and HGBCL/LBCL with 11q aberration, focusing on the differences between the two classifications. In the second part of the paper, we provide a practical diagnostic algorithm when facing LBCLs in routine daily practice.
Sugar Transport and Signaling in Shoot Branching
Authors: Doidy Joan , Wang Yuhui , Gouaille Léo , Goma-Louamba Ingrid , Jiang Zhengrong , Pourtau Nathalie , Le Gourrierec José , Sakr Soulaiman
Published: December 2024

The source–sink relationship is critical for proper plant growth and development, particularly for vegetative axillary buds, whose activity shapes the branching pattern and ultimately the plant architecture. Once formed from axillary meristems, axillary buds remain dormant or become active to grow into new branches. This transition is notably driven by the regulation of the bud sink strength, which is reflected in the ability to unload, metabolize and store photoassimilates. Plants have so far developed two main mechanisms for unloading sugars (sucrose) towards sink organs, a symplasmic pathway and an apoplasmic pathway, but so far limited investigations have been reported about the modes of sugar uptake during the transition from the dormant to the active outgrowth state of the bud. The available data indicate that the switch from dormant bud to active outgrowing state, requires sugar and is shortly preceded by an increase in bud metabolic activity and a remobilization of the stem starch reserves in favor of growing buds. This activation of the bud sink strength is accompanied by an up-regulation of the main markers of apoplasmic unloading, such as sugar transporters (sucrose transporters—SUTs; sugar will eventually be exported transporters—SWEETs), sucrose hydrolyzing enzymes (cell wall invertase—CWINV) and sugar metabolic pathways (glycolysis/tricarboxylic cycle—TCA; oxidative pentose phosphate pathway—OPPP). As these results are limited to a few species, they are not sufficient to provide a complete and accurate picture of the mode(s) of sugar unloading toward axillary buds and deserve to be complemented by additional studies in a wide variety of plants using systems integration, combining genetic, molecular and immunolocalization approaches. Altogether, we discuss here how sugar is a systemic regulator of shoot branching, acting both as an energy-rich molecule and a signaling entity in the establishment of the bud sink strength.
Integrated Transcriptomic and Proteomic Analyses of Antler Growth and Ossification Mechanisms
Authors: Liu Ruijia , Zhang Pan , Bai Jiade , Zhong Zhenyu , Shan Yunfang , Cheng Zhibin , Zhang Qingxun , Guo Qingyun , Zhang Hao , Zhang Bo
Published: December 2024

Antlers are the sole mammalian organs capable of continuous regeneration. This distinctive feature has evolved into various biomedical models. Research on mechanisms of antler growth, development, and ossification provides valuable insights for limb regeneration, cartilage-related diseases, and cancer mechanisms. Here, ribonucleic acid sequencing (RNA-seq) and four-dimensional data-independent acquisition (4D DIA) technologies were employed to examine gene and protein expression differences among four tissue layers of the Chinese milu deer antler: reserve mesenchyme (RM), precartilage (PC), transition zone (TZ), cartilage (CA). Overall, 4611 differentially expressed genes (DEGs) and 2388 differentially expressed proteins (DEPs) were identified in the transcriptome and proteome, respectively. Among the 828 DEGs common to both omics approaches, genes from the collagen, integrin, and solute carrier families, and signaling molecules were emphasized for their roles in the regulation of antler growth, development, and ossification. Bioinformatics analysis revealed that in addition to being regulated by vascular and nerve regeneration pathways, antler growth and development are significantly influenced by numerous cancer-related signaling pathways. This indicates that antler growth mechanisms may be similar to those of cancer cell proliferation and development. This study lays a foundation for future research on the mechanisms underlying the rapid growth and ossification of antlers.
OCTN1 (SLC22A4) as a Target of Heavy Metals: Its Possible Role in Microplastic Threats
Authors: Brunetti Luana S. , Scalise Mariafrancesca , Scanga Raffaella , Console Lara , Galluccio Michele , La Russa Mauro F. , Pochini Lorena , Indiveri Cesare
Published: December 2024

Microplastics represent a threat due to their ability to enter the food chain, with harmful consequences for living organisms. The riskiness of these particles is also linked to the release of other contaminants, such as heavy metals. Solute Carriers (SLCs) represent eminent examples of first-level targets of heavy metals due to their localization on the cell surface. Putative targets of heavy metals are the organic cation transporters that form a sub-clade of the SLC22 family. Besides the physiological role in the absorption/release of endogenous organic cations, these transporters are crucial in drug disposition and their interaction with xenobiotics. In this work, the human SLC22A4, commonly known as OCTN1, was used as a benchmark to test interactions with heavy metals released by microplastics, exploiting the proteoliposome tool. The potency of metals to interfere with the OCTN1 function has been evaluated by measuring IC50 values calculated in the micromolar range. The molecular mechanism of interaction has been defined using site-directed mutagenesis and computational analyses. Finally, some chemical and physiological thiol-reacting compounds show the capacity to rescue the metal-inhibited OCTN1 function. The conclusions drawn on OCTN1 can be extended to other members of the SLC22 family and orthologous transporters in fish.
Long-Term Yo-Yo Dieting Exaggerates Liver Steatosis and Lesions but Preserves Muscle Performance in Male Zebrafish
Authors: Hsu Tzu-Chieh , Chiang Chun-Hsien , Liu I-Hsuan , Wang Chih-Yun , Chen Ching-Yi
Published: December 2024

Weight regain within one year after weight loss is frequently observed and is referred to as yo-yo dieting or weight cycling. In this study, we explore the effects of yo-yo dieting on the liver, adipose tissue, and muscle characteristics of male zebrafish. Four-month-old AB wild-type male zebrafish were randomly assigned to three groups: high-calorie intake (H, seven meals per day), low-calorie intake (L, two meals per day), and yo-yo diet (the low- and high-calorie alternation switched every two weeks) groups. Feeding the fish the H diet for over 8 weeks led to steatosis and damage to the liver. The yo-yo diet reduced liver lipid accumulation at week eight but caused a similar degree of lipid accumulation as the H diet thereafter. It was found that twenty weeks of yo-yo dieting actually exacerbated hepatic damage. Compared to the L diet, feeding the fish on the yo-yo and H diets for a period of 20 weeks significantly increased the size of muscle fibers, resulting in higher speed during burst swimming and a significant increase in the size and number of adipocytes in the abdominal tissue. To summarize, short-term yo-yo dieting was found to attenuate hepatosteatosis and maintain fast-twitch muscle function. Long-term yo-yo dieting preserved fast-twitch muscle function and muscle fiber size; however, it exacerbated the pathological changes in the liver.
The Influence of Stakeholder Involvement in the Adoption of Digital Technologies in the UK Construction Industry
Authors: Hwabamungu Boroto , Shepherd Paul
Published: December 2024

This study explored stakeholder involvement practice in digitalisation of the construction industry in the UK, and the influence thereof in the adoption of digital technologies. A qualitative interpretive method was followed using a case study approach to collect data. Thematic analysis of twenty-four semi-structured interviews and sixty survey responses, which were conducted with different digital technologies adoption actors in the construction industry, allowed the identification of six final themes depicting the influence of stakeholder involvement in the adoption of digital technologies. The findings indicate that stakeholder involvement influence is a function of its embeddedness in an organisation digitalisation approach. Stakeholder involvement embeddedness in the approach, or lack thereof, dictates how the stakeholder landscape is planned and managed, and how communication between and with stakeholder groups occurs. This is the foundation of digitalisation value creation among stakeholders. The approach is prone to digitalisation limitations and intrinsic determinants of adoption, both of which can be positively impacted through better stakeholder involvement practices. Stakeholder involvement practices are therefore catalytic to the subsequent behaviour change for digital technologies adoption and the extent to which digital technologies become adopted. This paper contextualises stakeholder involvement in the adoption of digital technologies in the construction industry, highlighting the catalytic influence of stakeholder involvement embeddedness in the complex digitalisation activity system and its interplay with industry-specific practices and other digital technology adoption determinants.
Performance Assessment of Eco-Friendly Asphalt Binders Using Natural Asphalt and Waste Engine Oil
Authors: Albayati Amjad H. , Al-Kheetan Mazen J. , Mohammed Ahmed M. , Al-ani Aliaa F. , Moudhafar Mustafa M.
Published: December 2024

The depletion of petroleum reserves and increasing environmental concerns have driven the development of eco-friendly asphalt binders. This research investigates the performance of natural asphalt (NA) modified with waste engine oil (WEO) as a sustainable alternative to conventional petroleum asphalt (PA). The study examines NA modified with 10%, 20%, and 30% WEO by the weight of asphalt to identify an optimal blend ratio that enhances the binder’s flexibility and workability while maintaining high-temperature stability. Comprehensive testing was conducted, including penetration, softening point, viscosity, ductility, multiple stress creep recovery (MSCR), linear amplitude sweep (LAS), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). The results reveal that WEO effectively softens NA, improves ductility, and enhances workability, with the 20% WEO blend achieving the best balance of physical and rheological properties. Chemical analysis indicates that WEO increases carbon content and reduces sulfur and impurities, aligning NA’s composition closer to PA. However, excessive WEO (30%) compromises thermal stability and deformation resistance. The findings underscore the potential of WEO-modified NA for sustainable pavement applications, with 20% WEO identified as the optimal content to achieve performance comparable to conventional petroleum asphalt while promoting environmental sustainability.
AI in Structural Health Monitoring for Infrastructure Maintenance and Safety
Authors: Plevris Vagelis , Papazafeiropoulos George
Published: December 2024

This study explores the growing influence of artificial intelligence (AI) on structural health monitoring (SHM), a critical aspect of infrastructure maintenance and safety. This study begins with a bibliometric analysis to identify current research trends, key contributing countries, and emerging topics in AI-integrated SHM. We examine seven core areas where AI significantly advances SHM capabilities: (1) data acquisition and sensor networks, highlighting improvements in sensor technology and data collection; (2) data processing and signal analysis, where AI techniques enhance feature extraction and noise reduction; (3) anomaly detection and damage identification using machine learning (ML) and deep learning (DL) for precise diagnostics; (4) predictive maintenance, using AI to optimize maintenance scheduling and prevent failures; (5) reliability and risk assessment, integrating diverse datasets for real-time risk analysis; (6) visual inspection and remote monitoring, showcasing the role of AI-powered drones and imaging systems; and (7) resilient and adaptive infrastructure, where AI enables systems to respond dynamically to changing conditions. This review also addresses the ethical considerations and societal impacts of AI in SHM, such as data privacy, equity, and transparency. We conclude by discussing future research directions and challenges, emphasizing the potential of AI to enhance the efficiency, safety, and sustainability of infrastructure systems.
Active Components of 16 Essential Oils and Their Fumigation Effects on Galleria mellonella (Lepidoptera: Pyralidae)
Authors: Su Xiao-Ling , Huang Zhi-Chu , Chen Lin , Chen Dao-Yin , Zhao Dong-Xu , Zeng Zhi-Jiang
Published: December 2024

The greater wax moth (GWM, Galleria mellonella) is a prevalent pest of the honeybee and a significant risk to both honeybee populations and honeycomb storage. Research on the toxicity of essential oils (EOs) to GWM larvae has provided promising results, although their ovicidal effects and active ingredients require further study. Identifying effective plant compounds is essential for developing insecticides for GWM control. This study assessed the fumigation efficacy of 16 EOs on GWM eggs and fifth instar larvae and determined the effectiveness of these EOs and their primary components for fumigating fifth larvae. Wintergreen, star anise, and clove oils demonstrated significant insecticidal effects on GWM eggs and fifth instar larvae, resulting in a mortality rate exceeding 80% within 48 h. Gas chromatography-mass spectrometry analysis identified methyl salicylate (93.26%), trans-anethole (87.75%), and eugenol (77.75%) as the primary compounds in wintergreen, star anise, and clove oils, respectively. Further toxicity testing confirmed that these compounds were responsible for the observed insecticidal properties of the EOs. Notably, trans-anethole exhibited the lowest LC50 value (25.22 μL/L) against the fifth instar larvae of GWM and significant toxicity against GWM eggs and fifth instar larvae, suggesting its potential as a viable option for the future control of GWM populations.