bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding teaching behavior through a theoretical perspective of teacher conception: cases in China
Authors: Zhu Fangchun , Xu Binyan
Published: December 2023

Introduction

Teaching behavior is a key indicator for analyzing the cognitive factors of teachers. Cognitive factors affect teachers’ behavior. The use of technology rebuilds teachers’ didactical processes and their cognition in teaching mathematics.

Methods

This study examined classroom behavior from the perspective of teacher conception and chose the dynamic geometry software (DGS) to analyze how teacher conception affects their daily work by comparing four Chinese mathematics teachers with varying teaching and technology experiences.

Results

The results suggested that these teachers were aware of the value of the DGS in teaching and learning mathematics.

Discussion

Although it is still difficult for teachers to move away from the teacher-centered method, some have begun to use the DGS to create new learning situations with which students are not familiar to improve their mathematical skills. Further research is needed to obtain more evidence and generalized conclusions for other situations.
Enabling genome editing in tropical maize lines through an improved, morphogenic regulator-assisted transformation protocol
Authors: Hernandes-Lopes José , Pinto Maísa Siqueira , Vieira Letícia Rios , Monteiro Patrícia Brant , Gerasimova Sophia V. , Nonato Juliana Vieira Almeida , Bruno Maria Helena Faustinoni , Vikhorev Alexander , Rausch-Fernandes Fernanda , Gerhardt Isabel R. , Pauwels Laurens , Arruda Paulo , Dante Ricardo A. , Yassitepe Juliana Erika de Carvalho Teixeira
Published: December 2023

The recalcitrance exhibited by many maize (Zea mays) genotypes to traditional genetic transformation protocols poses a significant challenge to the large-scale application of genome editing (GE) in this major crop species. Although a few maize genotypes are widely used for genetic transformation, they prove unsuitable for agronomic tests in field trials or commercial applications. This challenge is exacerbated by the predominance of transformable maize lines adapted to temperate geographies, despite a considerable proportion of maize production occurring in the tropics. Ectopic expression of morphogenic regulators (MRs) stands out as a promising approach to overcome low efficiency and genotype dependency, aiming to achieve ’universal’ transformation and GE capabilities in maize. Here, we report the successful GE of agronomically relevant tropical maize lines using a MR-based, Agrobacterium-mediated transformation protocol previously optimized for the B104 temperate inbred line. To this end, we used a CRISPR/Cas9-based construct aiming at the knockout of the VIRESCENT YELLOW-LIKE (VYL) gene, which results in an easily recognizable phenotype. Mutations at VYL were verified in protoplasts prepared from B104 and three tropical lines, regardless of the presence of a single nucleotide polymorphism (SNP) at the seed region of the VYL target site in two of the tropical lines. Three out of five tropical lines were amenable to transformation, with efficiencies reaching up to 6.63%. Remarkably, 97% of the recovered events presented indels at the target site, which were inherited by the next generation. We observed off-target activity of the CRISPR/Cas9-based construct towards the VYL paralog VYL-MODIFIER, which could be partly due to the expression of the WUSCHEL (WUS) MR. Our results demonstrate efficient GE of relevant tropical maize lines, expanding the current availability of GE-amenable genotypes of this major crop.
MicroRNAs regulating macrophages infected with Leishmania L. (V.) Braziliensis isolated from different clinical forms of American tegumentary leishmaniasis
Authors: Lago Tainã , Medina Lilian , Lago Jamile , Santana Nadja , Cardoso Thiago , Rocha Alan , Leal-Calvo Thyago , Carvalho Edgar M. , Castellucci Léa Cristina
Published: December 2023

Background

Leishmaniasis is an infectious disease caused by protozoa of the genus Leishmania. There are still no vaccines, and therapeutic options are limited, indicating the constant need to understand the fine mechanisms of its pathophysiology. An approach that has been explored in leishmaniasis is the participation of microRNAs (miRNAs), a class of small non-coding RNAs that act, in most cases, to repress gene expression. miRNAs play a role in the complex and plastic interaction between the host and pathogens, either as part of the host’s immune response to neutralize infection or as a molecular strategy employed by the pathogen to modulate host pathways to its own benefit.

Methods

Monocyte-derived macrophages from healthy subjects were infected with isolates of three clinical forms of L. braziliensis: cutaneous (CL), mucosal (ML), and disseminated (DL) leishmaniasis. We compared the expression of miRNAs that take part in the TLR/NFkB pathways. Correlations with parasite load as well as immune parameters were analyzed.

Results

miRNAs -103a-3p, -21-3p, 125a-3p -155-5p, -146a-5p, -132- 5p, and -147a were differentially expressed in the metastatic ML and DL forms, and there was a direct correlation between miRNAs -103a-3p, -21-3p, -155-5p, -146a-5p, -132-5p, and -9-3p and parasite load with ML and DL isolates. We also found a correlation between the expression of miR-21-3p and miR-146a-5p with the antiapoptotic gene BCL2 and the increase of viable cells, whereas miR-147a was indirectly correlated with CXCL-9 levels.

Conclusion

The expression of miRNAs is strongly correlated with the parasite load and the inflammatory response, suggesting the participation of these molecules in the pathogenesis of the different clinical forms of L. braziliensis.
A community study of neutralizing antibodies against SARS-CoV-2 in China
Authors: Lv Yitong , Huang Lei , Wang Junhu , He Hui , Song Libo , He Jia , Xu Lida , Yu Changyuan , Mei Ying , Gao Qi
Published: December 2023

Background

The immune background of the overall population before and after the outbreak of SARS-CoV-2 in China remains unexplored. And the level of neutralizing antibodies is a reliable indicator of individual immunity.

Objectives

This study aimed to assess the immune levels of different population groups during a viral outbreak and identify the factors influencing these levels.

Methods

We measured the levels of neutralizing antibodies in 12,137 participants using the COVID19 Neutralizing Antibody Detection kit. The dynamics of neutralizing antibodies were analyzed using a generalized additive model, while a generalized linear model and multi-factor analysis of variance were employed to investigate the influencing factors. Additionally, statistical methods were used to compare neutralizing antibody levels among subgroups of the real-world population.

Results

Participants who received booster doses exhibited significantly higher levels of neutralizing antibodies compared to those who received only one or two doses (p<0.001). Both elderly [22.55 (5.12, 62.03) IU/mL, 55%] and minors [21.41 (8.15, 45.06) IU/mL, 56%] showed lower positivity rates and neutralizing antibody levels compared to young adults [29.30 (9.82, 188.08) IU/mL, 62%] (p<0.001). Furthermore, the HIV-positive group demonstrated a slightly lower seropositivity rate compared to the healthy group across the three vaccination time points. Notably, three months after the large-scale infection, both the neutralizing antibody level and positivity rate in real-world populations were higher than the previous record [300 (300, 300) IU/mL, 89%; 27.10 (8.77, 139.28) IU/mL, 60%], and this difference was statistically significant.

Conclusions

Increasing vaccine dosage enhances neutralizing antibody levels, resulting in greater and longer-lasting immunity. Monitoring immune levels in older individuals and those with AIDS is crucial. Additionally, the neutralizing antibodies generated from vaccination have not yet reached the threshold for achieving herd immunity, while individuals exhibit higher immune levels following a large-scale infection. These findings provide valuable insights for guiding new strategies in vaccine administration.
Modulatory immune responses in fungal infection associated with organ transplant - advancements, management, and challenges
Authors: Elalouf Amir , Elalouf Hadas , Rosenfeld Ariel
Published: December 2023

Organ transplantation stands as a pivotal achievement in modern medicine, offering hope to individuals with end-stage organ diseases. Advancements in immunology led to improved organ transplant survival through the development of immunosuppressants, but this heightened susceptibility to fungal infections with nonspecific symptoms in recipients. This review aims to establish an intricate balance between immune responses and fungal infections in organ transplant recipients. It explores the fundamental immune mechanisms, recent advances in immune response dynamics, and strategies for immune modulation, encompassing responses to fungal infections, immunomodulatory approaches, diagnostics, treatment challenges, and management. Early diagnosis of fungal infections in transplant patients is emphasized with the understanding that innate immune responses could potentially reduce immunosuppression and promise efficient and safe immuno-modulating treatments. Advances in fungal research and genetic influences on immune-fungal interactions are underscored, as well as the potential of single-cell technologies integrated with machine learning for biomarker discovery. This review provides a snapshot of the complex interplay between immune responses and fungal infections in organ transplantation and underscores key research directions.
The use of ketotifen as long-term anti-inflammatory prophylaxis in children with PFAPA syndrome
Authors: Kapustova Lenka , Banovcin Peter , Bobcakova Anna , Jurkova Malicherova Eva , Kapustova Daniela , Petrovicova Otilia , Slenker Branislav , Markocsy Adam , Oleksak Filip , Vorcakova Karolina , Jesenak Milos
Published: December 2023

Introduction

Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most frequent periodic fever syndrome in children. Its pathogenesis is still unknown, but some disease-modifying factors were observed. Several medications were tested for the long-term prophylaxis of inflammatory flares; however, none are standardly used.

Methods

This prospective clinical trial enrolled 142 children (71 girls, 50%) meeting diagnostic criteria for PFAPA syndrome. We analysed selected clinical characteristics and compared laboratory parameters during the flare and attack-free period (at least two weeks after the attack). Moreover, we assessed the possible therapeutic effect of ketotifen on the duration of attack free-periods and clinical picture.

Results

The mean age of patients was 6.81 ± 3.03 years and the mean age of onset of symptoms was 2.31 ± 2.02 years. No significant differences were observed between genders.We recorded a positive family history for PFAPA in 31.69% of patients. Attacks lasted for 2.8 ± 1.2 days, with intervals between attacks of 4 ± 1 weeks. We administered ketotifen in 111 (77.8%) patients, and a positive effect was observed in 86 (77.5%) of patients. We observed prolonged attack-free intervals in patients treated with ketotifen (14.7 ± 8.9 days in comparison with 4.4 ± 1.9 days before the treatment; p<0.001). The used dose of ketotifen was 0.08 ± 0.01 mg/kg/day. Mild side effects were observed in four patients (restlessness, irritability, agitation and constipation).

Discussion

Our data supports the use of ketotifen for long-term prophylaxis in children with PFAPA syndrome with positive effects on the attenuation of disease activity and the prolongation of attack-free periods. Further well-designed studies should confirm the preliminary data.
Roles of tissue-resident immune cells in immunotherapy of non-small cell lung cancer
Authors: Tang Rui , Wang Haitao , Tang Mingxi
Published: December 2023

Non-small cell lung cancer (NSCLC) is the most common and lethal type of lung cancer, with limited treatment options and poor prognosis. Immunotherapy offers hope for improving the survival and quality of life of NSCLC patients, but its efficacy depends on the tumor immune microenvironment (TME). Tissue-resident immune cells are a subset of immune cells that reside in various tissues and organs, and play an important role in fighting tumors. In NSCLC, tissue-resident immune cells are heterogeneous in their distribution, phenotype, and function, and can either promote or inhibit tumor progression and response to immunotherapy. In this review, we summarize the current understanding on the characteristics, interactions, and roles of tissue-resident immune cells in NSCLC. We also discuss the potential applications of tissue-resident immune cells in NSCLC immunotherapy, including immune checkpoint inhibitors (ICIs), other immunomodulatory agents, and personalized cell-based therapies. We highlight the challenges and opportunities for developing targeted therapies for tissue-resident immune cells and optimizing existing immunotherapeutic approaches for NSCLC patients. We propose that tissue-resident immune cells are a key determinant of NSCLC outcome and immunotherapy response, and warrant further investigation in future research.
Tracking the push towards extinction: combining dispersal and management data to monitor Asian longhorned beetle eradication in the U.S.
Authors: Trotter Robert Talbot , Ryan Josie K. , Chandler Jennifer L. , Pfister Scott
Published: December 2023

Introduction

Based on the threat posed by the Asian longhorned beetle (Anoplophora glabripennisMotschulsky), many countries including the United States have adopted policies of eradication. The eradication of infestations that cover hundreds of square kilometers can require multiple visual surveys of millions of individual trees. At these scales, eradication may take several decades and span multiple beetle generations. During this period the infestation of new trees adds spatially-explicit risk to the landscape while surveys and the removal of infested trees reduce it.

Methods

To track dynamic risk on the landscape we have developed the Asian Longhorned Beetle Hazard Management and Monitoring Tool. The geospatial tool combines data documenting; the locations, levels of infestation, and dates of detection of infested trees; the locations, methods, and timing of survey and host removal activities; and a reconstruction of beetle movement within the infested landscape to generate annual spatial estimates of infestation risk based on the combination of beetle dispersal and survey and host removal activities.

Results

The analyses of three eradication programs highlight similar patterns in risk through time with risk peaking at the time infestations are detected and declining as management activities slow beetle spread and reduce risk through surveys. However, the results also highlight differences in risk reduction among the eradication programs associated with differences in beetle dispersal among infestations and the size of the infested landscape, highlighting the importance of applying local information to structure eradication programs.

Discussion

The Asian Longhorned Beetle Hazard Management and Monitoring Tool provides a quantitative repeatable approach to tracking changes in infestation risk using local beetle behavior and management efforts. In addition to this, the tool may provide a structure to optimize eradication efforts by allowing managers to estimate expected risk reduction based on proposed survey and host removal strategies.
Revealing zooplankton diversity in the midnight zone
Authors: González Carolina E. , Blanco-Bercial Leocadio , Escribano Rubén , Fernández-Urruzola Igor , Rivera Reinaldo , Ulloa Osvaldo
Published: December 2023

Zooplankton diversity in the deep “midnight zone” (>1000 m), where sunlight does not reach, remains largely unknown. Uncovering such diversity has been challenging because of the major difficulties in sampling deep pelagic fauna and identifying many (unknown) species that belong to these complex swimmer assemblages. In this study, we evaluated zooplankton diversity using two taxonomic marker genes: mitochondrial cytochrome oxidase subunit 1 (COI) and nuclear 18S ribosomal RNA (18S). We collected samples from plankton net tows, ranging from the surface to a depth of 5000 m above the Atacama Trench in the Southeast Pacific. Our study aimed to assess the zooplankton diversity among layers from the upper 1000 m to the ultra-deep abyssopelagic zone to test the hypothesis of decreasing diversity with depth resulting from limited carbon sources. The results showed unique, highly vertically structured communities within the five depth strata sampled, with maximal species richness observed in the upper bathypelagic layer (1000–2000 m). The high species richness of zooplankton (>750 OTUS) at these depths was higher than that found in the upper 1000 m. The vertical diversity trend exhibited a pattern similar to the well-known vertical pattern described for the benthic system. However, a large part of this diversity was either unknown (>50%) or could not be assigned to any known species in current genetic diversity databases. DNA analysis showed that the Calanoid copepods, mostly represented by Subeucalanus monachus, the Euphausiacea, Euphausia mucronata, and the halocypridade, Paraconchoecia dasyophthalma, dominated the community. Water column temperature, dissolved oxygen, particulate carbon, and nitrogen appeared to be related to the observed vertical diversity pattern. Our findings revealed rich and little-known zooplankton diversity in the deep sea, emphasizing the importance of further exploration of this ecosystem to conserve and protect its unique biota.
Study on the nutritional composition of the sea vegetable Ulva compressa in a brine-based cultivation system
Authors: Fricke Anna , Harbart Vanessa , Schreiner Monika , Baldermann Susanne
Published: December 2023

Driven by the global need of alternative food sources, there is a rising interest in edible macroalgae (seaweeds). In order to provide fresh and healthy seafood even in inland areas, land-based, environmentally controlled seaweed farming is on the rise. Facing several issues, especially the need of suitable cultivation media increases with growing distance from the coast. In order to provide regional solutions and make the cultivation approaches more sustainable, the present study investigates the potential use of natural saline ground water (brine) for the production of the macroalga Ulva compressa in inland cultivation systems. Over a period of 88 days, macroalgal thalli were cultivated in aerated experimental units (120 L) filled with brine-based media or commercial artificial sea water. Physicochemical properties of the cultivation media and the nutritional profile of macroalgal thalli were analyzed after 52 and 88 days of cultivation. The results underline not only the feasibility to use brine in the farming of sea vegetables (e.g. overcoming the lack of seawater and reduction of freshwater use), but also clearly indicate a nutrional value for the U. compressa cultivation, resulting in algal thalli, rich in polyunsaturated fatty acids and carotenoids (e.g. lutein, β carotene). The present findings might serve as a step stone for the further development of brine-based inner land aquaculture systems.
Peripheral neutrophils and oxidative stress-associated molecules for predicting the severity of asthma: a cross-sectional study based on multidimensional assessment
Authors: Mao Ruolin , Jiang Zhilong , Min Zhihui , Wang Gang , Xie Min , Gao Peng , Zhu Lei , Li Huayin , Chen Zhihong
Published: December 2023

Objectives

This study aims to explore the relationship between the severity of asthma and neutrophils and related oxidative stress-associated molecules in peripheral blood and induced sputum.

Methods

A total of 67 subjects were included in this study, namely, 25 patients with severe asthma and 42 patients with non-severe asthma. Clinical data, induced sputum and peripheral blood were collected. Lung function and molecules related to oxidative stress in induced sputum and peripheral blood of asthma patients were detected. The relationship between neutrophils and asthma severity was analyzed. HDAC2 mRNA and protein expression levels and HDAC2 activity were also analyzed. Multivariate logistic regression was performed to select statistically significant variables.

Results

The absolute value of neutrophils and percentage of neutrophils were higher in the severe asthma patients. These two values were used to predict the severity of asthma by ROC analysis, with the best cutoff values being 4.55 × 109/L (sensitivity 83.3%, specificity 64.0%) and 55.15% (sensitivity 54.8%, specificity 88.0%). The ROS concentration of neutrophils in the induced sputum samples and the 8-iso-PGF2α concentration in the peripheral blood samples were higher in the severe asthma group (P = 0.012; P = 0.044), whereas there was reduced HDAC2 protein activity in PBMCs (P < 0.001). A logistic equation and a nomogram were created to give a precise prediction of disease severity.

Conclusion

Oxidative stress is increased in severe asthma patients. Peripheral blood neutrophils and 8-iso-PGF2α can be used as biomarkers to predict the severity of asthma. A prediction model was created for evaluating asthma severity.
Prediction model of adnexal masses with complex ultrasound morphology
Authors: Wu Yuqing , Miao Kuo , Wang Tianqi , Xu Changyu , Yao Jinlai , Dong Xiaoqiu
Published: December 2023

Background

Based on the ovarian-adnexal reporting and data system (O-RADS), we constructed a nomogram model to predict the malignancy potential of adnexal masses with sophisticated ultrasound morphology.

Methods

In a multicenter retrospective study, a total of 430 subjects with masses were collected in the adnexal region through an electronic medical record system at the Fourth Hospital of Harbin Medical University during the period of January 2019–April 2023. A total of 157 subjects were included in the exception validation cohort from Harbin Medical University Tumor Hospital. The pathological tumor findings were invoked as the gold standard to classify the subjects into benign and malignant groups. All patients were randomly allocated to the validation set and training set in a ratio of 7:3. A stepwise regression analysis was utilized for filtering variables. Logistic regression was conducted to construct a nomogram prediction model, which was further validated in the training set. The forest plot, C-index, calibration curve, and clinical decision curve were utilized to verify the model and assess its accuracy and validity, which were further compared with existing adnexal lesion models (O-RADS US) and assessments of different types of neoplasia in the adnexa (ADNEX).

Results

Four predictors as independent risk factors for malignancy were followed in the preparation of the diagnostic model: O-RADS classification, HE4 level, acoustic shadow, and protrusion blood flow score (all p < 0.05). The model showed moderate predictive power in the training set with a C-index of 0.959 (95%CI: 0.940–0.977), 0.929 (95%CI: 0.884–0.974) in the validation set, and 0.892 (95%CI: 0.843–0.940) in the external validation set. It showed that the predicted consequences of the nomogram agreed well with the actual results of the calibration curve, and the novel nomogram was clinically beneficial in decision curve analysis.

Conclusion

The risk of the nomogram of adnexal masses with complex ultrasound morphology contained four characteristics that showed a suitable predictive ability and provided better risk stratification. Its diagnostic performance significantly exceeded that of the ADNEX model and O-RADS US, and its screening performance was essentially equivalent to that of the ADNEX model and O-RADS US classification.
Probiotic and postbiotic analytical methods: a perspective of available enumeration techniques
Authors: Boyte Marie-Eve , Benkowski Andrzej , Pane Marco , Shehata Hanan R.
Published: December 2023

Probiotics are the largest non-herbal/traditional dietary supplements category worldwide. To be effective, a probiotic strain must be delivered viable at an adequate dose proven to deliver a health benefit. The objective of this article is to provide an overview of the various technologies available for probiotic enumeration, including a general description of each technology, their advantages and limitations, and their potential for the future of the probiotics industry. The current “gold standard” for analytical quantification of probiotics in the probiotic industry is the Plate Count method (PC). PC measures the bacterial cell’s ability to proliferate into detectable colonies, thus PC relies on cultivability as a measure of viability. Although viability has widely been measured by cultivability, there has been agreement that the definition of viability is not limited to cultivability. For example, bacterial cells may exist in a state known as viable but not culturable (VBNC) where the cells lose cultivability but can maintain some of the characteristics of viable cells as well as probiotic properties. This led to questioning the association between viability and cultivability and the accuracy of PC in enumerating all the viable cells in probiotic products. PC has always been an estimate of the number of viable cells and not a true cell count. Additionally, newer probiotic categories such as Next Generation Probiotics (NGPs) are difficult to culture in routine laboratories as NGPs are often strict anaerobes with extreme sensitivity to atmospheric oxygen. Thus, accurate quantification using culture-based techniques will be complicated. Another emerging category of biotics is postbiotics, which are inanimate microorganisms, also often referred to as tyndallized or heat-killed bacteria. Obviously, culture dependent methods are not suitable for these products, and alternative methods are needed for their quantification. Different methodologies provide a more complete picture of a heterogeneous bacterial population versus PC focusing exclusively on the eventual multiplication of the cells. Alternative culture-independent techniques including real-time PCR, digital PCR and flow cytometry are discussed. These methods can measure viability beyond cultivability (i.e., by measuring cellular enzymatic activity, membrane integrity or membrane potential), and depending on how they are designed they can achieve strain-specific enumeration.
Phylogenetic analysis, morphological studies, element profiling, and muscarine detection reveal a new toxic Inosperma (Inocybaceae, Agaricales) species from tropical China
Authors: Zhou Yu-Ling , Deng Lun-Sha , Yang Shu-Dong , Liu Chao-Feng , Fan Yu-Guang , Yu Wen-Jie
Published: December 2023

Tropical Asian collections of Inosperma are usually poisonous mushrooms that have caused many poisoning incidents. However, the species diversity and the toxic mechanisms of these Inosperma species are still unclear. In this study, we describe the discovery of Inosperma wuzhishanense sp. nov. from Wuzhishan City, Hainan Province, tropical China. The new species was identified based on morphological and multi-locus (ITS, nrLSU, and RPB2) phylogenetic analyses. The new species is characterized by its reddish-brown pileus, fibrillose stipes with finely protruding fibrils, rather crowded lamellae, smooth and ellipsoid basidiospores, and mostly clavate, thin-walled cheilocystidia. The new species is phylogenetically nested in the Old World tropical clade 2 and is sister to the tropical Indian taxa I. akirnum. Detailed descriptions, color photos of the new species, and comparisons with its closely related species are provided. Additionally, the muscarine content of the new species was analyzed by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC–MS/MS). The muscarine contents ranged from 4,359.79 ± 83.87 mg/kg to 7,114.03 ± 76.55 mg/kg, 2,748.37 ± 106.85 mg/kg to 4,491.35 ± 467.21 mg/kg, and 2,301.36 ± 83.52 mg/kg to 2,775.90 ± 205.624 mg/kg in the stipe, pileus, and lamellae, respectively. The elemental composition and concentration were determined using inductively coupled plasma-mass spectrometry (ICP-MS). A total of 24 elements were detected. Among the heavy metals detected, arsenic showed the highest level of toxicity with a concentration of 36.76 ± 0.43 mg/kg.
Evidence of DISC1 as an arsenic binding protein and implications regarding its role as a translational activator
Authors: Watanabe Muneaki , Khu Tung Mei , Warren Grant , Shin Juyoung , Stewart Charles E. , Roche Julien
Published: December 2023

Disrupted-in-schizophrenia-1 (DISC1) is a scaffolding protein that plays a pivotal role in orchestrating signaling pathways involved in neurodevelopment, neural migration, and synaptogenesis. Among those, it has recently been reported that the role of DISC1 in the Akt/mTOR pathway can shift from a global translational repressor to a translational activator in response to oxidative stress induced by arsenic. In this study we provide evidence that DISC1 can directly bind arsenic via a C-terminal cysteine motif (C-X-C-X-C). A series of fluorescence-based binding assays were conducted with a truncated C-terminal domain construct of DISC1 and a series of single, double, and triple cysteine mutants. We found that arsenous acid, a trivalent arsenic derivative, specifically binds to the C-terminal cysteine motif of DISC1 with low micromolar affinity. All three cysteines of the motif are required for high-affinity binding. Electron microscopy experiments combined with in silico structural predictions reveal that the C-terminal of DISC1 forms an elongated tetrameric complex. The cysteine motif is consistently predicted to be located within a loop, fully exposed to solvent, providing a simple molecular framework to explain the high-affinity of DISC1 toward arsenous acid. This study sheds light on a novel functional facet of DISC1 as an arsenic binding protein and highlights its potential role as both a sensor and translational modulator within Akt/mTOR pathway.
Crosstalk of ferroptosis and oxidative stress in infectious diseases
Authors: Hu Yibao , He Bisha , Cao Qian , Li Yue , Tang Yun , Cao Ting , Peng Binfeng , Zhou Xiangping , Liu Shuangquan
Published: December 2023

Ferroptosis is a type of programmed cell death that pathogens can leverage to enhance their replication, transmission, and pathogenicity. Hosts typically combat pathogenic infections by utilizing oxidative stress as a defense mechanism. Nonetheless, some pathogens can trigger considerable oxidative stress while infecting, inducing an intense inflammatory response in the host’s immune system and activating cell death. The process of ferroptosis is closely linked to oxidative stress, with their interaction exerting a substantial impact on the outcome of infectious diseases. This article presents an overview of the interrelated mechanisms of both Ferroptosis and oxidative stress in infectious diseases, identifying potential targets for treating such diseases in the context of their interaction.
Altered synaptic plasticity at hippocampal CA1–CA3 synapses in Alzheimer's disease: integration of amyloid precursor protein intracellular domain and amyloid beta effects into computational models
Authors: Dainauskas Justinas J. , Vitale Paola , Moreno Sebastien , Marie Hélène , Migliore Michele , Saudargiene Ausra
Published: December 2023

Alzheimer's disease (AD) is a progressive memory loss and cognitive dysfunction brain disorder brought on by the dysfunctional amyloid precursor protein (APP) processing and clearance of APP peptides. Increased APP levels lead to the production of AD-related peptides including the amyloid APP intracellular domain (AICD) and amyloid beta (Aβ), and consequently modify the intrinsic excitability of the hippocampal CA1 pyramidal neurons, synaptic protein activity, and impair synaptic plasticity at hippocampal CA1–CA3 synapses. The goal of the present study is to build computational models that incorporate the effect of AD-related peptides on CA1 pyramidal neuron and hippocampal synaptic plasticity under the AD conditions and investigate the potential pharmacological treatments that could normalize hippocampal synaptic plasticity and learning in AD. We employ a phenomenological N-methyl-D-aspartate (NMDA) receptor-based voltage-dependent synaptic plasticity model that includes the separate receptor contributions on long-term potentiation (LTP) and long-term depression (LTD) and embed it into the a detailed compartmental model of CA1 pyramidal neuron. Modeling results show that partial blockade of Glu2NB-NMDAR-gated channel restores intrinsic excitability of a CA1 pyramidal neuron and rescues LTP in AICD and Aβ conditions. The model provides insight into the complex interactions in AD pathophysiology and suggests the conditions under which the synchronous activation of a cluster of synaptic inputs targeting the dendritic tree of CA1 pyramidal neuron leads to restored synaptic plasticity.
Efficacy and safety of magnetic resonance-guided focused ultrasound for Parkinson’s disease: a systematic review and meta-analysis
Authors: Tian Xiaona , Hu Rongrui , He Peicong , Ye Jianhong
Published: December 2023

Objective

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a novel noninvasive treatment for drug-resistant Parkinson’s disease (PD) related tremor. This study aims to evaluate MRgFUS’s efficacy and safety in PD through a systematic review and meta-analysis, examining pre-and post-treatment MDS-UPDRSIII and/or CRST scores and associated adverse events.

Materials and methods

We conducted an extensive literature search across PubMed, Embase, Web of Science, and Cochrane Library databases, screening studies based on set criteria and analyzing MDS-UPDRSIII, CRST, and adverse events pre- and post-MRgFUS treatment.

Results

Out of 468 retrieved articles, 20 studies involving 258 patients, spanning 2014–2023, were included.17 studies indicated significant MDS-UPDRSIII score reductions post-MRgFUS treatment, while 3 showed significant CRST score declines. In the “on” medication state, pooled MDS-UPDRSIII scores at 1, 3, 6, and 12 months were 12.18 (95% CI: 5.83–18.52), 12.10 (95% CI: 8.22–15.97), 14.85 (95% CI: 9.28–20.41), and 20.65 (95% CI: 12.15–29.14) respectively. In the “off” state, scores were 11.45 (95% CI: −3.50-26.40), 14.71 (95% CI: 4.95–24.46), 21.52 (95% CI: 19.28–23.75), and 22.28 (95% CI: 15.26–29.30). Adverse events were typically mild and transient, with speech disturbances, ataxia, and sensory abnormalities being common post-operative neurological complications.

Conclusion

MRgFUS offers an effective and relatively safe treatment option for patients with drug-resistant PD-related tremor.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, No. CRD42023428332.
Impact of endocrine dysregulation on disability and non-motor symptoms in pediatric onset multiple sclerosis
Authors: Abe Justin , Jafarpour Saba , Vu My H. , O'Brien Devon , Boyd Natalie K. , Vogel Benjamin N. , Nguyen Lina , Paulsen Kelli C. , Saucier Laura E. , Ahsan Nusrat , Mitchell Wendy G. , Santoro Jonathan D.
Published: December 2023

Background

Pediatric onset multiple sclerosis (POMS) commonly occurs at the time of various endocrine changes. Evaluation of the impact of endocrine status on disease severity in POMS has not been previously explored.

Objective

This study sought to evaluate if sex and stress hormones in children with POMS impact motor and non-motor diseases severity.

Methods

A single-center case control study was performed. Individuals with POMS were compared to individuals without neurologic disease. Each individual had three blood draws assessing stress and sex hormones between 07:00 and 09:00. Measures of fatigue (Epworth sleepiness scale), depression (PHQ-9), and quality of life (PedsQL) assessed at each visit.

Results

Forty individuals with POMS and 40 controls were enrolled. Individuals with POMS had lower free testosterone (p = 0.003), cortisol (p < 0.001), and ACTH (p < 0.001) and had higher progesterone (p = 0.025) levels than controls. Relapses and EDSS were not impacted by endocrine variables. The POMS cohort had a significantly higher Epworth score (p < 0.001), PHQ-9 score (p < 0.001), and lower PQL score (p < 0.001) than controls. Non-motor measures were not associated with endocrine status.

Conclusion

Free testosterone, cortisol, ACTH, and progesterone were abnormal in children with POMS although there was no association between endocrine status and markers of disease severity or non-motor symptoms of MS.
Construct validity of a dietary protein assessment questionnaire to explore college students’ knowledge and attitudes towards dietary protein
Authors: Gutjahr Parker , Warren Cynthia , Miketinas Derek
Published: December 2023

Introduction

Misconceptions about dietary protein may exist due to unscientific information from commonly used sources such as social media. Understanding knowledge and attitudes towards protein is important for developing effective interventions to improve the dietary behaviors of U.S. college students. The objective of this study was to develop a questionnaire to evaluate college students’ knowledge and attitudes towards dietary protein.

Methods

The questionnaire had 64 questions, including 8 demographic, 24 knowledge, 14 attitude, and 18 behavior questions. Construct validity of the knowledge questions was assessed by performing known-group comparisons using an independent t-test. Exploratory factor analysis (EFA) with principal axis factoring and a promax rotation was used to evaluate the factor structure of the attitude questions.

Results

Four hundred seventy participants (87.3% female) provided responses for the attitude questions. Fifty-five nutrition and Fifty-one non-nutrition students provided responses for the knowledge questions. Three factors were retained: animal protein sources’ relationship with human and environmental health (Factor 1); organic protein sources (Factor 2); and adequacy of the protein recommended dietary allowance (RDA) for weight loss and vegetarian diets (Factor 3). Mean knowledge responses were 66.4 ± 11.5% and 47.6 ± 16.4% for nutrition and non-nutrition students, respectively (t-testp-value for difference <0.001).

Conclusion

Protein attitudes appear multidimensional and correlated. Further testing is needed to confirm the three-factor model and to assess temporal reliability.
Butyrate suppresses experimental necrotizing enterocolitis–induced brain injury in mice
Authors: Martinez Maribel , Yu Wei , Menden Heather L. , Lei Tianhua , Monaghan-Nichols Paula , Sampath Venkatesh
Published: December 2023

Background

Necrotizing enterocolitis (NEC) is a devastating disease in premature infants, and 50% of infants with surgical NEC develop neurodevelopmental defects. The mechanisms by which NEC-induced cytokine release and activation of inflammatory cells in the brain mediate neuronal injury, and whether enteral immunotherapy attenuates NEC-associated brain injury remain understudied. Based on our prior work, which demonstrated that experimental NEC-like intestinal injury is attenuated by the short-chain fatty acid, butyrate, in this study, we hypothesize that NEC-induced brain injury would be suppressed by enteral butyrate supplementation.

Methods

A standardized NEC mouse model [enteral formula feeding, lipopolysaccharide (LPS), and hypoxia] was used. Mice were randomized into the following groups: control, NEC, butyrate pretreated NEC, and butyrate control. NEC scoring (1–4 with 4 representing severe injury) was performed on ileal sections using a validated scoring system. Intestinal and brain lysates were used to assess inflammation, proinflammatory signaling, and apoptosis.

Results

NEC-induced intestinal injury was attenuated by butyrate supplementation. NEC-induced microglial activation in the cerebral cortex and hippocampus was suppressed with butyrate. NEC increased the number of activated microglial cells but decreased the number of oligodendrocytes. Butyrate pretreatment attenuated these changes. Increased activation of proinflammatory Toll-like receptor signaling, cytokine expression, and induction of GFAP and IBA1 in the cerebral cortex observed with NEC was suppressed with butyrate.

Conclusion

Experimental NEC induced inflammation and activation of microglia in several regions of the brain, most prominently in the cortex. NEC-induced neuroinflammation was suppressed with butyrate pretreatment. The addition of short-chain fatty acids to diet may be used to attenuate NEC-induced intestinal injury and neuroinflammation in preterm infants.
The antibacterial effectiveness of lavender essential oil against methicillin-resistant Staphylococcus aureus: a systematic review
Authors: Truong Sandra , Mudgil Poonam
Published: December 2023

With the overuse and misuse of antibiotics, multi-drug resistant organisms have become a prominent issue in healthcare, increasing morbidity and mortality in affected patients. One such organism of concern is methicillin-resistant Staphylococcus aureus (MRSA) which is a leading cause of a variety of clinical infections. Therefore, in the interest of finding alternate substances to antibiotics, there has been increased interest in the antibacterial properties of lavender essential oil (LEO). This systematic review aims to collate information regarding the antibacterial properties of LEO against S. aureus and MRSA. A systematic search was conducted across four databases between the years 2002 and 2022, and through this, 23 studies were included in this paper. These studies used a variety of methods to ascertain the antibacterial effectiveness of LEO alone or in combination with other substances. Overall, there were mixed results regarding the antibacterial effectiveness of LEO against S. aureus and MRSA, with some studies reporting significant effectiveness, while other studies reporting a minimal to negligible effect. However, findings suggest that LEO works synergistically with other antibacterial substances, and it would be beneficial for additional research to be conducted in this area.
Enhanced central sympathetic tone induces heart failure with preserved ejection fraction (HFpEF) in rats
Authors: Nandi Shyam S. , Katsurada Kenichi , Moulton Michael J. , Zheng Hong , Patel Kaushik P.
Published: December 2023

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome characterized by diastolic dysfunction, concentric cardiac left ventricular (LV) hypertrophy, and myocardial fibrosis with preserved systolic function. However, the underlying mechanisms of HFpEF are not clear. We hypothesize that an enhanced central sympathetic drive is sufficient to induce LV dysfunction and HFpEF in rats. Male Sprague–Dawley rats were subjected to central infusion of either saline controls (saline) or angiotensin II (Ang II, 20 ng/min, i.c.v) via osmotic mini-pumps for 14 days to elicit enhanced sympathetic drive. Echocardiography and invasive cardiac catheterization were used to measure systolic and diastolic functions. Mean arterial pressure, heart rate, left ventricular end-diastolic pressure (LVEDP), and ± dP/dt changes in responses to isoproterenol (0.5 μg/kg, iv) were measured. Central infusion of Ang II resulted in increased sympatho-excitation with a consequent increase in blood pressure. Although the ejection fraction was comparable between the groups, there was a decrease in the E/A ratio (saline: 1.5 ± 0.2 vs Ang II: 1.2 ± 0.1). LVEDP was significantly increased in the Ang II-treated group (saline: 1.8 ± 0.2 vs Ang II: 4.6 ± 0.5). The increase in +dP/dt to isoproterenol was not significantly different between the groups, but the response in -dP/dt was significantly lower in Ang II-infused rats (saline: 11,765 ± 708 mmHg/s vs Ang II: 8,581 ± 661). Ang II-infused rats demonstrated an increased heart to body weight ratio, cardiomyocyte hypertrophy, and fibrosis. There were elevated levels of atrial natriuretic peptide and interleukin-6 in the Ang II-infused group. In conclusion, central infusion of Ang II in rats induces sympatho-excitation with concurrent diastolic dysfunction, pathological cardiac concentric hypertrophy, and cardiac fibrosis. This novel model of centrally mediated sympatho-excitation demonstrates characteristic diastolic dysfunction in rats, representing a potentially useful preclinical murine model of HFpEF to investigate various altered underlying mechanisms during HFpEF in future studies.
Response of leaf functional traits to soil nutrients in the wet and dry seasons in a subtropical forest on an island
Authors: Zhang Juanjuan , Liang Minxia , Tong Sen , Qiao Xueting , Li Buhang , Yang Qiong , Chen Ting , Hu Ping , Yu Shixiao
Published: December 2023

Introduction

Island ecosystems often have a disproportionate number of endemic species and unique and fragile functional characteristics. However, few examples of this type of ecosystem have been reported.

Methods

We conducted a comprehensive field study on Neilingding Island, southern China. The leaf samples of 79 subtropical forest tree species were obtained and their functional traits were studied in the dry and wet seasons to explain the relationships between plant functional traits and soil nutrients.

Results

We found a greater availability of soil moisture content (SMC) and nutrients in the wet season than in the dry season. The values of wet season soil available phosphorus (5.97 mg·kg−1), SMC (17.67%), and soil available potassium (SAK, 266.96 mg·kg−1) were significantly higher than those of the dry season. The leaf dry matter content, specific leaf weight, leaf density, leaf total carbon, leaf total nitrogen, leaf total calcium, and the N/P and C/P ratios of leaves were all significantly higher in the dry season than in the wet season, being 18.06%, 12.90%, 12.00%, 0.17%, 3.41%, 9.02%, 26.80%, and 24.14% higher, respectively. In contrast, the leaf area (51.01 cm2), specific leaf area (152.76 cm2·g−1), leaf water content (0.59%), leaf total nitrogen (1.31%), leaf total phosphorus (0.14%), and leaf total magnesium (0.33%) were much lower in the dry season than in the wet one. There were significant pairwise correlations between leaf functional traits, but the number and strength of correlations were significantly different in the dry and wet seasons. The SAK, soil total phosphorus (STP), and pH impacted plant leaf functional traits in the dry season, whereas in the wet season, they were affected by SAK, STP, pH, and NO3− (nitrate).

Discussion

Both soil nutrients and water availability varied seasonally and could cause variation in a number of leaf traits.