bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing β-Galactosidase Performance for Galactooligosaccharides Preparation via Strategic Glucose Re-Tunneling
Authors: Zhao Jihua , Niu Dandan , Liu Jiaqi , Jin Zhuolin , Mchunu Nokuthula Peace , Singh Suren , Wang Zhengxiang
Published: November 2024

This study focuses on the characterization and re-engineering of glucose transport in β-galactosidase (BglD) to enhance its catalytic efficiency. Computational prediction methods were employed to identify key residues constituting access tunnels for lactose and glucose, revealing distinct pockets for both substrates. In silico simulated saturation mutagenesis of residues T215 and T473 led to the identification of eight mutant variants exhibiting potential enhancements in glucose transport. Site-directed mutagenesis at T215 and T473 resulted in mutants with consistently enhanced specific activities, turnover rates, and catalytic efficiencies. These mutants also demonstrated improved galactooligosaccharide (GOS) synthesis, yielding an 8.1–10.6% enhancement over wild-type BglD yield. Structural analysis revealed that the mutants exhibited transformed configurations and localizations of glucose conduits, facilitating expedited glucose release. This study’s findings suggest that the re-engineered mutants offer promising avenues for enhancing BglD’s catalytic efficiency and glucose translocation, thereby improving GOS synthesis. By-product (glucose) re-tunneling is a viable approach for enzyme tunnel engineering and holds significant promise for the molecular evolution of enzymes.
Broad Neutralization Capacity of an Engineered Thermostable Three-Helix Angiotensin-Converting Enzyme 2 Polypeptide Targeting the Receptor-Binding Domain of SARS-CoV-2
Authors: Cavazzini Davide , Levati Elisabetta , Germani Saveria , Ta Bao Loc , Monica Lara , Bolchi Angelo , Donofrio Gaetano , Garrapa Valentina , Ottonello Simone , Montanini Barbara
Published: November 2024

The mutational drift of SARS-CoV-2 and the appearance of multiple variants, including the latest Omicron variant and its sub-lineages, has significantly reduced (and in some cases abolished) the protective efficacy of Wuhan spike-antigen-based vaccines and therapeutic antibodies. One of the most functionally constrained and thus largely invariable regions of the spike protein is the one involved in the interaction with the ACE2 receptor mediating the cellular entry of SARS-CoV-2. Engineered ACE2, both as a full-length protein or as an engineered polypeptide fragment, has been shown to be capable of preventing the host-cell binding of all viral variants and to be endowed with potent SARS-CoV-2 neutralization activity both in vitro and in vivo. Here, we report on the biochemical and antiviral properties of rationally designed ACE2 N-terminal, three-helix fragments that retain a native-like conformation. One of these fragments, designated as PRP8_3H and produced in recombinant form, bears structure-stabilizing and binding-affinity enhancing mutations in α-helix-I and in both α-helix I and II, respectively. While the native-like, unmodified three α-helices ACE2 fragment proved to be thermally unstable and without any detectable pseudovirion neutralization capacity, PRP8_3H was found to be highly thermostable and capable of binding to the SARS-CoV-2 spike receptor-binding domain with nanomolar affinity and to neutralize both Wuhan and Omicron spike-expressing pseudovirions at (sub)micromolar concentrations. PRP8_3H thus lends itself as a highly promising ACE2 decoy prototype suitable for a variety of formulations and prophylactic applications.
The Involvement of Glial Cells in Blood–Brain Barrier Damage in Neuroimmune Diseases
Authors: Nagata Satoshi , Yamasaki Ryo
Published: November 2024

The blood–brain barrier and glial cells, particularly astrocytes, interact with each other in neuroimmune diseases. In the inflammatory environment typical of these diseases, alterations in vascular endothelial cell surface molecules and weakened cell connections allow immune cells and autoantibodies to enter the central nervous system. Glial cells influence the adhesion of endothelial cells by changing their morphology and releasing various signaling molecules. Multiple sclerosis has been the most studied disease in relation to vascular endothelial and glial cell interactions, but these cells also significantly affect the onset and severity of other neuroimmune conditions, including demyelinating and inflammatory diseases. In this context, we present an overview of these interactions and highlight how they vary across different neuroimmune diseases.
Insights into the Identification of iPSC- and Monocyte-Derived Macrophage-Polarizing Compounds by AI-Fueled Cell Painting Analysis Tools
Authors: Brüggenthies Johanna B. , Dittmer Jakob , Martin Eva , Zingman Igor , Tabet Ibrahim , Bronner Helga , Groetzner Sarah , Sauer Julia , Dehghan Harati Mozhgan , Scharnowski Rebekka , Bakker Julia , Riegger Katharina , Heinzelmann Caroline , Ast Birgit , Ries Robert , Fillon Sophie A. , Bachmayr-Heyda Anna , Kitt Kerstin , Grundl Marc A. , Heilker Ralf , Humbeck Lina , Schuler Michael , Weigle Bernd
Published: November 2024

Macrophage polarization critically contributes to a multitude of human pathologies. Hence, modulating macrophage polarization is a promising approach with enormous therapeutic potential. Macrophages are characterized by a remarkable functional and phenotypic plasticity, with pro-inflammatory (M1) and anti-inflammatory (M2) states at the extremes of a multidimensional polarization spectrum. Cell morphology is a major indicator for macrophage activation, describing M1(-like) (rounded) and M2(-like) (elongated) states by different cell shapes. Here, we introduced cell painting of macrophages to better reflect their multifaceted plasticity and associated phenotypes beyond the rigid dichotomous M1/M2 classification. Using high-content imaging, we established deep learning- and feature-based cell painting image analysis tools to elucidate cellular fingerprints that inform about subtle phenotypes of human blood monocyte-derived and iPSC-derived macrophages that are characterized as screening surrogate. Moreover, we show that cell painting feature profiling is suitable for identifying inter-donor variance to describe the relevance of the morphology feature ‘cell roundness’ and dissect distinct macrophage polarization signatures after stimulation with known biological or small-molecule modulators of macrophage (re-)polarization. Our novel established AI-fueled cell painting analysis tools provide a resource for high-content-based drug screening and candidate profiling, which set the stage for identifying novel modulators for macrophage (re-)polarization in health and disease.
Psychiatric Symptoms in Wilson’s Disease—Consequence of ATP7B Gene Mutations or Just Coincidence?—Possible Causal Cascades and Molecular Pathways
Authors: Gromadzka Grażyna , Antos Agnieszka , Sorysz Zofia , Litwin Tomasz
Published: November 2024

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism. The genetic defect in WD affects the ATP7B gene, which encodes the ATP7B transmembrane protein, which is essential for maintaining normal copper homeostasis in the body. It is primarily expressed in the liver and acts by incorporating copper into ceruloplasmin (Cp), the major copper transport protein in the blood. In conditions of excess copper, ATP7B transports it to bile for excretion. Mutations in ATP7B lead to impaired ATP7B function, resulting in copper accumulation in hepatocytes leading to their damage. The toxic “free”—unbound to Cp—copper released from hepatocytes then accumulates in various organs, contributing to their damage and clinical manifestations of WD, including hepatic, neurological, hematological, renal, musculoskeletal, ophthalmological, psychiatric, and other effects. While most clinical manifestations of WD correspond to identifiable organic or cellular damage, the pathophysiology underlying its psychiatric manifestations remains less clearly understood. A search for relevant articles was conducted in PubMed/Medline, Science Direct, Scopus, Willy Online Library, and Google Scholar, combining free text and MeSH terms using a wide range of synonyms and related terms, including “Wilson’s disease”, “hepatolenticular degeneration”, “psychiatric manifestations”, “molecular mechanisms”, “pathomechanism”, and others, as well as their combinations. Psychiatric symptoms of WD include cognitive disorders, personality and behavioral disorders, mood disorders, psychosis, and other mental disorders. They are not strictly related to the location of brain damage, therefore, the question arises whether these symptoms are caused by WD or are simply a coincidence or a reaction to the diagnosis of a genetic disease. Hypotheses regarding the etiology of psychiatric symptoms of WD suggest a variety of molecular mechanisms, including copper-induced CNS toxicity, oxidative stress, mitochondrial dysfunction, mitophagy, cuproptosis, ferroptosis, dysregulation of neurotransmission, deficiencies of neurotrophic factors, or immune dysregulation. New studies on the expression of noncoding RNA in WD are beginning to shed light on potential molecular pathways involved in psychiatric symptomatology. However, current evidence is still insufficient to definitively establish the cause of psychiatric symptoms in WD. It is possible that the etiology of psychiatric symptoms varies among individuals, with multiple biological and psychological mechanisms contributing to them simultaneously. Future studies with larger samples and comprehensive analyses are necessary to elucidate the mechanisms underlying the psychiatric manifestations of WD and to optimize diagnostics and therapeutic approaches.
Interaction Between Early Meals (Big-Breakfast Diet), Clock Gene mRNA Expression, and Gut Microbiome to Regulate Weight Loss and Glucose Metabolism in Obesity and Type 2 Diabetes
Authors: Jakubowicz Daniela , Matz Yael , Landau Zohar , Rosenblum Rachel Chava , Twito Orit , Wainstein Julio , Tsameret Shani
Published: November 2024

The circadian clock gene system plays a pivotal role in coordinating the daily rhythms of most metabolic processes. It is synchronized with the light–dark cycle and the eating–fasting schedule. Notably, the interaction between meal timing and circadian clock genes (CGs) allows for optimizing metabolic processes at specific times of the day. Breakfast has a powerful resetting effect on the CG network. A misaligned meal pattern, such as skipping breakfast, can lead to a discordance between meal timing and the endogenous CGs, and is associated with obesity and T2D. Conversely, concentrating most calories and carbohydrates (CH) in the early hours of the day upregulates metabolic CG expression, thus promoting improved weight loss and glycemic control. Recently, it was revealed that microorganisms in the gastrointestinal tract, known as the gut microbiome (GM), and its derived metabolites display daily oscillation, and play a critical role in energy and glucose metabolism. The timing of meal intake coordinates the oscillation of GM and GM-derived metabolites, which in turn influences CG expression, playing a crucial role in the metabolic response to food intake. An imbalance in the gut microbiota (dysbiosis) can also reciprocally disrupt CG rhythms. Evidence suggests that misaligned meal timing may cause such disruptions and can lead to obesity and hyperglycemia. This manuscript focuses on the reciprocal interaction between meal timing, GM oscillation, and circadian CG rhythms. It will also review studies demonstrating how aligning meal timing with the circadian clock can reset and synchronize CG rhythms and GM oscillations. This synchronization can facilitate weight loss and improve glycemic control in obesity and those with T2D.
Physiological and Molecular Mechanisms of Lepidopteran Insects: Genomic Insights and Applications of Genome Editing for Future Research
Authors: Niu Dongsheng , Zhao Qing , Xu Linbo , Lin Kejian
Published: November 2024

Lepidopteran insects are a major threat to global agriculture, causing significant crop losses and economic damage. Traditional pest control methods are becoming less effective due to the rapid evolution of insecticide resistance. This study explores the current status and genomic characteristics of 1315 Lepidopteran records, alongside an overview of relevant research, utilizing advanced functional genomics techniques, including RNA-seq and CRISPR/Cas9 gene-editing technologies to uncover the molecular mechanisms underlying insecticide resistance. Our genomic analysis revealed significant variability in genome size, assembly quality, and chromosome number, which may influence species’ biology and resistance mechanisms. We identified key resistance-associated genes and pathways, including detoxification and metabolic pathways, which help these insects evade chemical control. By employing CRISPR/Cas9 gene-editing techniques, we directly manipulated resistance-associated genes to confirm their roles in resistance, demonstrating their potential for targeted interventions in pest management. These findings emphasize the value of integrating genomic data into the development of effective and sustainable pest control strategies, reducing reliance on chemical insecticides and promoting environmentally friendly integrated pest management (IPM) approaches. Our study highlights the critical role of functional genomics in IPM and its potential to provide long-term solutions to the growing challenge of Lepidopteran resistance.
Planar-Twisted Molecular Engineering for Modulating the Fluorescence Brightness of NIR-II Fluorophores with a Donor–Acceptor–Donor Skeleton
Authors: Ji Shengjiao , Du Yuying , Leng Jiancai , Zhang Yujin , Hu Wei
Published: November 2024

Organic molecular fluorophores have been extensively utilized for biological imaging in the visible and the first near-infrared windows. However, their applications in the second near-infrared (NIR-II) window remain constrained, primarily due to the insufficient fluorescence brightness. Herein, we employ a theoretical protocol combining the thermal vibration correlation function with the time-dependent density functional theory method to investigate the mechanism of the planar-twisted strategy for developing fluorophores with balanced NIR-II emission and fluorescence brightness. Based on a planar donor–acceptor–donor molecular skeleton, various ortho-positioned alkyl side chains with steric hindrances are tactfully incorporated into the backbone to construct a series of twisted fluorophores. Photophysical characterizations of the studied fluorophores demonstrate that the emission spectra located in the NIR-II region exhibited a hypsochromic shift with the structural distortion. Notably, conformational twisting significantly accelerated the radiative decay rate while simultaneously suppressing the nonradiative decay rate, resulting in an improved fluorescence quantum efficiency (FQE). This enhancement can be mainly attributed to both the enlarged adiabatic excitation energy and reduced nonadiabatic electronic coupling between the first excited state and the ground state. Compared with the planar fluorophore, the twisted structures possessed a more than fivefold increase in FQE. In particular, the optimal twisted fluorophore BBTD-4 demonstrated a desirable fluorescence brightness (16.59 M−1 cm−1) on the premise of typical NIR-II emission (980 nm), making it a promising candidate for NIR-II fluorescence imaging in biomedical applications. The findings in this study elucidate the available experimental observations on the analogues, highlighting a feasible approach to modulating the photophysical performances of NIR-II chromophores for developing more highly efficient fluorophores toward optical imaging applications.
Gene Therapy for Parkinson’s Disease Using Midbrain Developmental Genes to Regulate Dopaminergic Neuronal Maintenance
Authors: Kim Jintae , Chang Mi-Yoon
Published: November 2024

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by the progressive loss of dopaminergic (DAnergic) neurons in the substantia nigra and decreased dopamine (DA) levels, which lead to both motor and non-motor symptoms. Conventional PD treatments aim to alleviate symptoms, but do not delay disease progression. PD gene therapy offers a promising approach to improving current treatments, with the potential to alleviate significant PD symptoms and cause fewer adverse effects than conventional therapies. DA replacement approaches and DA enzyme expression do not slow disease progression. However, DA replacement gene therapies, such as adeno-associated virus (AAV)–glutamic acid decarboxylase (GAD) and L-amino acid decarboxylase (AADC) gene therapies, which increase DA transmitter levels, have been demonstrated to be safe and efficient in early-phase clinical trials. Disease-modifying strategies, which aim to slow disease progression, appear to be potent. These include therapies targeting downstream pathways, neurotrophic factors, and midbrain DAnergic neuronal factors, all of which have shown potential in preclinical and clinical trials. These approaches focus on maintaining the integrity of DAnergic neurons, not just targeting the DA transmitter level itself. In particular, critical midbrain developmental and maintenance factors, such as Nurr1 and Foxa2, can interact synergistically with neighboring glia, in a paracrine mode of action, to protect DAnergic neurons against various toxic factors. Similar outcomes could be achieved by targeting both DAnergic neurons and glial cells with other candidate gene therapies, but in-depth research is needed. Neurotrophic factors, such as neurturin, the glial-cell-line-derived neurotrophic factor (GDNF), the brain-derived neurotrophic factor (BDNF), and the vascular endothelial growth factor (VEGF), are also being investigated for their potential to support DAnergic neuron survival. Additionally, gene therapies targeting key downstream pathways, such as the autophagy–lysosome pathway, mitochondrial function, and endoplasmic reticulum (ER) stress, offer promising avenues. Gene editing and delivery techniques continue to evolve, presenting new opportunities to develop effective gene therapies for PD.
How Agroecological Transition Frameworks Are Reshaping Agroecology: A Review
Authors: Fonseca Ana Filipa , Polita Fabíola , Madureira Lívia
Published: November 2024

The “agroecological transition” has emerged as a framework that aims to explain the complex changes taking place in agrifood systems. This study offers a mapping of the emergence of this framework, and aims to demonstrate that the agroecological transition can refer to different perspectives beyond the simple combination of two concepts. We carried out a bibliometric analysis of 298 articles (2012–2023), searched using the command “agroecologic* transition*”. We used VOSviewer software (version 1.6.20), which is able to reveal clusters of co-citations of the most cited authors and articles. This result, in turn, indicates the existence of different perspectives on the use of agroecological transitions. Four clusters were found: (i) “Techniques and Practices”, represented by articles that document the agroecological transition as an expression of specific agricultural techniques and practices; (ii) “Transition Theory”, which employs the emerging theory and its conceptual contributions; (iii) “Transition Criteria”, which involves the use of criteria to monitor the transition; and (iv) “Political and Social”, made up of articles that explore the political and social movement dimension of agroecology. Each of these clusters, and their approaches, contribute different interpretations of agroecology itself, indicating the emergence of a new framework capable of attributing new meanings to it.
A Multi-Objective Optimization Framework for Coupled Grey–Green Infrastructure of Areas with Contamination-Induced Water Shortages Under Future Multi-Dimensional Scenarios
Authors: Xu Zixiang , Cheng Jiaqing , Xu Haishun , Li Jining
Published: November 2024

Stormwater resource utilization is an important function of coupled grey–green infrastructure (CGGI) that has received little research focus, especially in multi-objective optimization studies. Given the complex water problems in areas with contamination-induced water shortages, it is important to incorporate more objectives into optimization systems. Therefore, this study integrated economic performance, hydrological recovery, water quality protection, and stormwater resource utilization into an optimization framework based on the non-dominant sorting genetic algorithm III (NSGA-III). A sponge city pilot area with contamination-induced water shortages in the Yangtze River Delta was considered, optimizing four objectives under different future multi-dimensional scenarios. The results showed a time series and scenarios composed of shared socioeconomic pathways and representative concentration pathways (SSP-RCP scenarios) which, together, affected future climate change and the benefits of a CGGI. In the near and middle periods, the SSP126 scenario had the greatest influence on stormwater management, whereas, in the far period, the SSP585 scenario had the greatest influence. The far period had the greatest influence under three SSP-RCP scenarios. Under the combined influence of SSP-RCP scenarios and a time series, the SSP585-F scenario had the greatest impact. Specific costs could be used to achieve different and no stormwater-resource utilization effects through different configurations of the CGGI. This provided various construction ideas regarding CGGIs for areas with contamination-induced water shortages.
Spatial Optimization and Sustainable Development of Land Use
Authors: He Qingsong , Zheng Linzi , Zhou Peng , Zhou Jiang
Published: November 2024

As global urbanization accelerates and climate change intensifies, issues related to land use and management have increasingly garnered attention within the international academic community [...]
Spatiotemporal Dynamics and Driving Factors of Soil Salinization: A Case Study of the Yutian Oasis, Xinjiang, China
Authors: Li Shiqin , Nurmemet Ilyas , Seydehmet Jumeniyaz , Lv Xiaobo , Aili Yilizhati , Yu Xinru
Published: November 2024

Soil salinization is a critical global environmental issue, exacerbated by climatic and anthropogenic factors, and posing significant threats to agricultural productivity and ecological stability in arid regions. Therefore, remote sensing-based dynamic monitoring of soil salinization is crucial for timely assessment and effective mitigation strategies. This study used Landsat imagery from 2001 to 2021 to evaluate the potential of support vector machine (SVM) and classification and regression tree (CART) models for monitoring soil salinization, enabling the spatiotemporal mapping of soil salinity in the Yutian Oasis. In addition, the land use transfer matrix and spatial overlay analysis were employed to comprehensively analyze the spatiotemporal trends of soil salinization. The geographical detector (Geo Detector) tool was used to explore the driving factors of the spatiotemporal evolution of salinization. The results indicated that the CART model achieved 5.3% higher classification accuracy than the SVM, effectively mapping the distribution of soil salinization and showing a 26.76% decrease in salinized areas from 2001 to 2021. Improvements in secondary salinization and increased vegetation coverage were the primary contributors to this reduction. Geo Detector analysis highlighted vegetation (NDVI) as the dominant factor, and its interaction with soil moisture (NDWI) has a significant impact on the spatial and temporal distribution of soil salinity. This study provides a robust method for monitoring soil salinization, offering critical insights for effective salinization management and sustainable agricultural practices in arid regions.
The Outdoor Area Implications of Mixed Housing Tenure Initiatives—A Swedish Case in Tynnered, Gothenburg
Authors: Biddulph Robin , Sandberg Mattias
Published: November 2024

Mixing tenure types is often seen as a means of reducing segregation by breaking up concentrations of poverty. Previous research suggests that introducing new tenure types may also result in homeowners erecting fences and attempting to control activity by public housing tenants in outdoor spaces. These have often meant that tenure mix rather than reducing segregation has instead inscribed it within neighbourhoods. We conducted a case study of a mixed-tenure neighbourhood in Sweden, relying primarily on resident interviews. The results were analysed thematically using the concepts of nested commons, gentrification of outdoor space, and a smorgasbord of places. We found some evidence of new fencing and of attempts to modify shared outdoor area use, but overall, relations remained harmonious. We argue that this was largely because the smorgasbord of places created by the original planners has largely remained intact, and because there were not sharp social differences between the residents of the different tenure forms. Nevertheless, we argue that the outdoor implications of tenure mix initiatives can be crucial to the outcomes of such initiatives, and that they deserve serious attention from policymakers and practitioners.
Laparoscopic Cholecystectomy Under Combined Spinal and Epidural Anesthesia in the First Trimester of Pregnancy—Case Report and Literature Review
Authors: Gorecki Gabriel-Petre , Bodor Andrei , Kövér Zoltan-Janos , Comănici Maria-Mihaela , Sima Romina-Marina , Panaitescu Anca-Maria , Comănici Adrian-Vasile , Furdu-Lungut Emilia , Constantin Ancuta-Alina , Pleș Liana , Diaconescu Andrei Sebastian , Lungu Vasile
Published: November 2024

Can combined spinal and epidural anesthesia be the gold standard for laparoscopic surgery for pregnant patients? This case report presents a first trimester pregnant patient who was admitted for obstructive jaundice syndrome (pain in the right hypochondrium, nausea, and vomiting). Initially, because of the risk/benefit ratio of pregnancy, the treatment was medical and the patient was immediately discharged because her clinical condition improved, but she was rapidly readmitted to the surgery department because of worsening symptoms. Emergency surgical intervention (laparoscopic cholecystectomy) under combined spinal and epidural anesthesia (CSEA) was performed to reduce the patient’s risks. Since most analgesics are insufficiently studied in pregnancy, analgesia with ropivacaine 0.2% was used on the epidural catheter. No pathological changes were identified in the fetal Doppler ultrasound preoperatively and postoperatively. Similarly to other studies, our case highlights the necessity for cholecystectomy for acute cholecystitis even if the patient is in the first trimester of pregnancy. If the decision is delayed, the morbidity and mortality for mother and fetus become unjustified. The peculiarity of the present report is the type of anesthesia chosen. We consider that combined spinal and epidural anesthesia may become a possible gold standard suitable for laparoscopy in the first trimester of pregnancy.
Development of Imaging Complexity Biomarkers for Prediction of Symptomatic Radiation Pneumonitis in Patients with Non-Small Cell Lung Cancer, Focusing on Underlying Lung Disease
Authors: Hwang Jeongeun , Kim Hakyoung , Moon Joon-Young , Kim Sun Myung , Yang Dae Sik
Published: November 2024

Objectives: We aimed to develop imaging biomarkers to predict radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients undergoing thoracic radiotherapy. We hypothesized that measuring morphometric complexity in the lung using simulation computed tomography may provide objective imaging biomarkers for lung parenchyma integrity, potentially forecasting the risk of RP. Materials and Methods: A retrospective study was performed on medical records of 175 patients diagnosed with NSCLC who had received thoracic radiotherapy. Three indices were utilized to measure the morphometric complexity of the lung parenchyma: box-counting fractal dimension, lacunarity, and minimum spanning tree (MST) fractal dimension. Patients were dichotomized into two groups at median values. Cox proportional hazard models were constructed to estimate the hazard ratios for grade ≥ 2 or grade ≥ 3 RP. Results and Conclusions: We found significant associations between lung parenchymal morphometric complexity and RP incidence. In univariate Cox-proportional hazard analysis, patients with a lower MST fractal dimension had a significantly higher hazard ratio of 2.296 (95% CI: 1.348–3.910) for grade ≥ 2 RP. When adjusted for age, sex, smoking status, category of the underlying lung disease, category of radiotherapy technique, clinical stage, histology, and DLCO, patients with a lower MST fractal dimension showed a significantly higher hazard ratio of 3.292 (95% CI: 1.722–6.294) for grade ≥ 2 RP and 7.952 (95% CI: 1.722 36.733) for grade ≥ 3 RP than those with a higher MST fractal dimension. Patients with lower lacunarity exhibited a significantly lower hazard ratio of 0.091 (95% CI: 0.015–0.573) for grade ≥ 3 RP in the adjusted model. We speculated that the lung tissue integrity is captured by morphometric complexity measures, particularly by the MST fractal dimension. We suggest the MST fractal dimension as an imaging biomarker for predicting the occurrence of symptomatic RP after thoracic radiotherapy.
The Potential of Agaricus bisporus in Mitigating Pesticide-Induced Oxidative Stress in Honey Bees Infected with Nosema ceranae
Authors: Jelisić Stefan , Stanimirović Zoran , Ristanić Marko , Nakarada Đura , Mojović Miloš , Bošnjaković Dušan , Glavinić Uroš
Published: November 2024

Global climate change, environmental pollution, and frequent pesticide use severely reduce bee populations, greatly challenging beekeeping. Pesticides such as deltamethrin, a pyrethroid insecticide commonly used to control mosquitoes, can kill individual bees and entire colonies, depending on the exposure. Due to mosquito resistance to pyrethroid insecticides, components that enhance their effect are commonly used. This study explores the potential of Agaricus bisporus mushroom extract in mitigating oxidative stress in bees triggered by pesticides and Nosema ceranae infection. Our findings indicate that A. bisporus extract significantly reduced mortality rates of bees and spore counts of N. ceranae. Furthermore, the extract demonstrated antioxidant properties that lower enzyme activity related to oxidative stress (CAT, SOD, and GST) and MDA concentration, which is linked to lipid peroxidation. These results indicate that natural extracts like A. bisporus can aid bee health by mitigating the effects of pesticides and pathogens on honey bees, thus improving biodiversity.
In Vitro Evaluation of Iraqi Kurdistan Tomato Accessions Under Drought Stress Conditions Using Polyethylene Glycol-6000
Authors: Tahir Nawroz Abdul-razzak , Rasul Kamaran Salh , Lateef Djshwar Dhahir , Aziz Rebwar Rafat , Ahmed Jalal Omer
Published: November 2024

Drought is one of the major abiotic stresses that affect plant growth and productivity, and plant stress responses are affected by both the intensity of stress and genotype. In Iraqi Kurdistan, tomato plants play a significant role in the country’s economy. Due to climate change, which causes soil moisture to diminish, the crop’s growth and yield have been dropping in recent years. Accordingly, the effects of simulated drought stress on germination parameters were assessed in 64 tomato accessions gathered from the Iraqi Kurdistan region in order to identify sensitive and tolerant accessions. In this respect, the responses associated with drought stress were observed phenotypically and biochemically. Germination percentage (GP) and morphological characteristics such as root length (RL), shoot length (SL), and shoot fresh weight (SFW) were significantly reduced in both stress treatments with polyethylene glycol (PEG-6000) (7.5% PEG and 15% PEG). On the other hand, significant changes in biochemical profiles such as proline content (PC), soluble sugar content (SSC), total phenolic content (TPC), antioxidant activity (AC), guaiacol peroxidase (GPA), catalase (CAT), and lipid peroxidation (LP) in tomato accessions were detected; all biochemical traits were increased in most tomato accessions under the PEG-induced treatments compared to the control treatment (0.0% PEG). Three tomato accessions (AC61 (Raza Pashayi), AC9 (Wrdi Be Tow), and AC63 (Sandra)) were found to be the most tolerant accessions under all drought conditions, whereas the performances of the other tested accessions (AC13 (Braw), AC30 (Yadgar), and AC8 (Israili)) were inferior. The OMIC analysis identified the biomarker parameters for differentiating the highly, moderately, and low tolerant groups as PC, SSC, and TPC. This study shows that early PEG-6000 screening for drought stress may help in choosing a genotype that is suitable for growth in water-stressed environments. Hence, Raza Pashayi, Wrdi Be Tow, and Sandra accessions, which had great performances under drought conditions, can be candidates for selection in a breeding program to improve the growth of plants and production in the areas that face water limits.
PiCCO or Cardiac Ultrasound? Which Is Better for Hemodynamic Monitoring in ICU?
Authors: Andrei Maria , Dragoescu Nicoleta Alice , Stanculescu Andreea , Chiutu Luminita , Dragoescu Octavian , Istratoaie Octavian
Published: November 2024

Advanced hemodynamic monitoring is fundamental in the management of the critically ill. Blood pressure and cardiac function are key markers of cardiovascular system function;, thus, having accurate measurements of these parameters in critically ill patients is essential. Currently, there are various methods available to choose from, as well as a greater understanding of the methods and criteria to be able to compare devices and select the best option for our patients’ needs. Cardiac ultrasound and transpulmonary thermodilution help tailor the therapy for a patient’s individual needs by putting the results of a thorough hemodynamic assessment into context. Both these hemodynamic monitoring techniques have their advantages, drawbacks and limitations. Cardiac ultrasound is a safe, non-invasive, less expensive, efficient bedside tool for diagnosing, monitoring and guiding critically ill patients’ therapy management. It is recommended in the consensus guidelines as the first-choice method, especially when it comes to identifying different types of shock or the various factors involved. Pulse index contour continuous cardiac output (PiCCO) is a minimally invasive hemodynamic monitoring technique, integrating various static and hemodynamic parameters through a combination of trans-cardiopulmonary thermodilution and pulse contour analysis. The PiCCO method provides guidance to fluid and vasoactive therapy in critically ill patients and is also used for intraoperative and postoperative fluid management and monitoring in cardiac surgery. While invasive methods such as PiCCO are recommended for hemodynamic monitoring and can provide accurate information, they are not always necessary and are contraindicated in some cases.
One-Step Multiplex RT-PCR Method for Detection of Melon Viruses
Authors: Han Sheng , Zhou Tingting , Zhang Fengqin , Feng Jing , Han Chenggui , Maimaiti Yushanjiang
Published: November 2024

This study presents a one-step multiplex reverse transcription polymerase chain reaction (RT-PCR) method for the simultaneous detection of multiple viruses affecting melon crops. Viruses such as Watermelon mosaic virus (WMV), Cucumber mosaic virus (CMV), Zucchini yellow mosaic virus (ZYMV), Squash mosaic virus (SqMV), Tobacco mosaic virus (TMV), Papaya ring spot virus (PRSV), and Melon yellow spot virus (MYSV) pose a great threat to melons. The mixed infection of these viruses is the most common observation in the melon-growing fields. In this study, we surveyed northern Xingjiang (Altay, Changji, Wujiaqu, Urumqi, Turpan, and Hami) and southern Xingjiang (Aksu, Bayingolin, Kashgar, and Hotan) locations in Xinjiang province and developed a one-step multiplex RT-PCR to detect these melon viruses. The detection limits of this multiplex PCR were 103 copies/μL for ZYMV and MYSV and 102 copies/μL for WMV, SqMV, PRSV, CMV, and TMV. The detection results in the field showed 242 samples were infected by one or more viruses. The multiplex RT-PCR protocol demonstrated rapid, simultaneous, and relatively effective detection of viruses such as WMV, CMV, ZYMV, SqMV, TMV, PRSV, and MYSV. The technique is designed to identify these melon viruses in a single reaction, enhancing diagnostic efficiency and reducing costs, thus serving as a reference for muskmelon anti-virus breeding in Xinjiang.
Cast from the Past? Microbial Diversity of a Neolithic Stone Circle
Authors: Martín-Cereceda Mercedes , de Cos-Gandoy Amaya , Williams Richard A. J. , Elliott David , Serrano-Bellón Andrea , Pérez-Uz Blanca , Sanchez-Jimenez Abel
Published: November 2024

We studied the microbial diversity colonizing limestone rock pools at a Neolithic Monument (Arbor Low, Derbyshire, England). Five pools were analyzed: four located at the megaliths of the stone circle and one pool placed at the megalith at the Gib Hill burial mound 300 m distant. Samples were taken from rock pool walls and sediments, and investigated through molecular metabarcoding. The microbiome consisted of 23 phyla of bacteria (831 OTUs), 4 phyla of archaea (19 OTUs), and 27 phyla of microbial eukarya (596 OTUs). For bacteria, there were statistically significant differences in wall versus sediment populations, but not between pools. For archaea and eukarya, significant differences were found only between pools. The most abundant bacterial phylum in walls was Cyanobacteriota, and Pseudomonadota in sediments. For archaea and microbial eukarya, the dominant phyla were Euryarcheota and Chlorophyta, respectively, in both wall and sediments. The distant pool (P5) showed a markedly different community structure in phyla and species, habitat discrimination, and CHN content. Species sorting and dispersal limitation are discussed as mechanisms structuring the microbiome assemblages and their spatial connectivity. The Arbor Low microbiome is composed of terrestrial representatives common in extreme environments. The high presence of Cyanobacteriota and Chlorophyta in the Arbor Low stones is troubling, as these microorganisms can induce mechanical disruption by penetrating the limestone matrix through endolithic/chasmoendolithic growth. Future research should focus on the metabolic traits of strains to ascertain their implication in bioweathering and/or biomineralization.
Identification of Mycoplasma Species in Cattle Associated with Bovine Respiratory Disease Mortality
Authors: Carella Emanuele , Messana Erika , Mugetti Davide , Biasibetti Elena , Pezzolato Marzia , Peletto Simone , Begovoeva Mattia , Rossi Francesca
Published: November 2024

Approximately 30 distinct Mycoplasma species have been isolated from cattle, but only a few are pathogenic and can cause serious respiratory diseases. Consequently, this study aimed to identify Mycoplasma spp. infections in cattle with bovine respiratory disease (BRD), considering factors such as animal demographics, concurrent infections with other pathogens, post-mortem clinical findings and histological examinations, and seasonality. A total of 326 samples were collected from 322 cattle that had died from BRD in Northwestern Italy. A total of 54 animals (16.8%) tested positive for Mycoplasma spp., and Mycoplasma bovis (n = 22, 40.7%) and Mycoplasma dispar (n = 13, 24.1%) were the most frequently detected species among the examined cattle. Among positive cattle, those aged five months or younger were approximately five times more likely to be infected by Mycoplasma dispar than by Mycoplasma bovis compared to those older than five months (proportional incidence ratio: 5.1, 95% CI 1.2–21.2). The main bacterial pathogens identified in cattle exhibiting co-infection was Pasteurella multocida, whereas the main viral pathogens were BRSV and BoHV-1. Histopathological investigations predominantly revealed catarrhal bronchopneumonia or purulent catarrhal bronchopneumonia among the examined cattle. Finally, Mycoplasma hyopharyngis, a species isolated from the pharyngeal and nasal cavities of pigs so far, was detected for the first time in the pneumonic lung of a bovine infected with BRD. Further investigations are necessary to thoroughly characterize its host range and pathogenic potential.
Protective Role of Indole-3-Acetic Acid Against Salmonella Typhimurium: Inflammation Moderation and Intestinal Microbiota Restoration
Authors: Fan Yuxin , Song Qinglong , Li Siyu , Tu Jiayu , Yang Fengjuan , Zeng Xiangfang , Yu Haitao , Qiao Shiyan , Wang Gang
Published: November 2024

Indole-3-acetic acid (IAA), a metabolite derived from microbial tryptophan metabolism, plays a crucial role in regulating intestinal homeostasis. However, the influence and potential applications of IAA in the context of animal pathogen infections remain underexplored. This study investigates the prophylactic effects of IAA pretreatment against Salmonella typhimurium (ST) SL1344 infection, focusing on its ability to attenuate inflammatory responses, enhance intestinal barrier integrity, inhibit bacterial colonization, and restore colonic microbiota dysbiosis. The results demonstrated that IAA ameliorated the clinical symptoms in mice, as evidenced by reduced weight loss and histopathological damage. Furthermore, IAA inhibited the inflammatory response by downregulating the gene expression of pro-inflammatory cytokines IL-17A, TNF-α, IL-1β, and IL-6 in colon, ileum, and liver. IAA also preserved the integrity of the intestinal mucosal barrier and promoted the expression of tight junction proteins. Additionally, 16S rRNA gene sequencing revealed significant alterations in intestinal microbiota structure induced by ST infection following IAA treatment. Notable changes in β diversity and species richness were characterized by the enrichment of beneficial bacteria including Bacteroideaceae, Spirillaceae, and Bacillus. The proliferation of Salmonella enterica subspecies enterica serovar Typhi was significantly inhibited, thereby enhancing the intestinal health of the host. In summary, the oral administration of IAA contributes to the alleviation of inflammation, restoration of the intestinal barrier, and correction of colonic microbiota disturbance in mice challenged with ST.
Response of Yields, Soil Physiochemical Characteristics, and the Rhizosphere Microbiome to the Occurrence of Root Rot Caused by Fusarium solani in Ligusticum chuanxiong Hort.
Authors: Sun Xiaofang , Liu Yong , He Lian , Kuang Zaiyin , Dai Shundong , Hua Lixia , Jiang Qiuping , Wei Taiyang , Ye Pengsheng , Zeng Hualan
Published: November 2024

Ligusticum chuanxiong Hort. is considered an important medicinal herb with extremely high economic value and medicinal value due to its various effects, including anti-oxidation, sedative action, hepatoprotection, and invigorating blood circulation. However, L. chuanxiong cultivation is hampered by various plant diseases, especially the root rot caused by Fusarium solani, hindering the sustainable development of the L. chuanxiong industry. The occurrence of soil-borne diseases is closely linked to imbalances in the microbial community structure. Here, we studied the yields, rhizosphere microbiota, and soil physiochemical characteristics of healthy and diseased L. chuanxiong plants affected by root rot with high-throughput sequencing and microbial network analysis, aiming to explore the relationships between soil environmental factors, microbiomes, and plant health of L. chuanxiong. According to the results, L. chuanxiong root rot significantly decreased the yields, altered microbial community diversity and composition, enriched more pathogenic fungi, recruited some beneficial bacteria, and reduced microbial interaction network stability. The Mantel test showed that soil organic matter and pH were the major environmental factors modulating plant microbiome assembly. The root rot severity was significantly affected by soil physiochemical properties, including organic matter, cation exchange capacity, available nitrogen, phosphorus, potassium, and pH. Furthermore, two differential microbes that have great potential in the biocontrol of L. chuanxiong root rot were dug out in the obtained results, which were the genera Trichoderma and Bacillus. This study provided a theoretical basis for further studies revealing the microecological mechanism of L. chuanxiong root rot and the ecological prevention and control of L. chuanxiong root rot from a microbial ecology perspective.
Quantifying the Molecular Properties of the Elk Chronic Wasting Disease Agent with Mass Spectrometry
Authors: Silva Christopher J. , Erickson-Beltran Melissa L. , Cassmann Eric D. , Greenlee Justin J.
Published: November 2024

Chronic wasting disease (CWD) is a prion disease afflicting wild and farmed elk. CWD prions (PrPSc) are infectious protein conformations that replicate by inducing a natively expressed prion protein (PrPC) to refold into the prion conformation. Mass spectrometry was used to study the prions resulting from a previously described experimental inoculation of MM132, ML132, and LL132 elk with a common CWD inoculum. Chymotryptic digestion times and instrument parameters were optimized to yield a set of six peptides, TNMK, MLGSAMSRPL, LLGSAMSRPL, ENMYR, MMER, and VVEQMCITQYQR. These peptides were used to quantify the amount, the M132 and L132 polymorphic composition, and the extent of methionine oxidation of elk PrPSc. The amount (ng/g brain tissue) of PrPSc present in each sample was determined to be: MM132 (5.4 × 102 ± 7 × 101), ML132 (3.3 × 102 ± 6 × 101 and 3.6 × 102 ± 3 × 101) and LL132 (0.7 × 102 ± 1 × 101, 0.2 × 102 ± 0.2 × 101, and 0.2 × 102 ± 0.5 × 101). The proportion of L132 polymorphism in ML132 (heterozygous) PrPSc from CWD-infected elk was determined to be 43% ± 2% or 36% ± 3%. Methionine oxidation was detected and quantified for the M132 and L132 polymorphisms in the samples. In this way, mass spectrometry can be used to characterize prion strains at a molecular level.
Kinetics of RPR Decline in Pregnant Persons Treated for Syphilis in Pregnancy and Their Infants
Authors: Schwartz Danielle , Tse-Chang Alena , Robinson Joan , Gratrix Jennifer , Smyczek Petra , Hawkes Michael T.
Published: November 2024

Congenital syphilis is a re-emerging infectious threat in areas of North America. The purpose of this study was to quantitatively describe the rate of decline of nontreponemal (rapid plasma reagin, RPR) titers in pregnant persons with syphilis and their infants. In a retrospective review, we included 120 pregnant persons with 563 reactive RPR measurements (median 5, range 2 to 11 per person) and 35 infants with 81 RPR measurements (median 2, range 2 to 6 per infant). First-order decay, second-order decay, and a mathematical model representing functional FcRn-mediated antibody recycling were fitted to individual patient RPR trajectories. The RPR titers decreased with a median half-life of 39 days (IQR 28–59) and 27 days (IQR 17–41) in birthing parents and infants, respectively. The half-life varied with the initial RPR titer, suggesting that the kinetics of RPR decline was not first-order. A mathematical model accounting for saturable antibody recycling explained the longevity of RPR reactivity, predicted the observed non-linear kinetics, and fit the empiric data well. In summary, RPR titers decline with a half-life of roughly one month; however, the elimination does not follow first-order kinetics. Saturable antibody recycling may explain the prolonged and non-linear elimination of nontreponemal antibodies.