bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic control of type III interferon expression by 8-oxoguanine and its reader 8-oxoguanine DNA glycosylase1
Authors: Xue Yaoyao , Pan Lang , Vlahopoulos Spiros , Wang Ke , Zheng Xu , Radak Zsolt , Bacsi Attila , Tanner Lloyd , Brasier Allan R. , Ba Xueqing , Boldogh Istvan
Published: August 2023

Interferons (IFNs) are secreted cytokines with the ability to activate expression of IFN stimulated genes that increase resistance of cells to virus infections. Activated transcription factors in conjunction with chromatin remodelers induce epigenetic changes that reprogram IFN responses. Unexpectedly, 8-oxoguanine DNA glycosylase1 (Ogg1) knockout mice show enhanced stimuli-driven IFN expression that confers increased resistance to viral and bacterial infections and allergen challenges. Here, we tested the hypothesis that the DNA repair protein OGG1 recognizes 8-oxoguanine (8-oxoGua) in promoters modulating IFN expression. We found that functional inhibition, genetic ablation, and inactivation by post-translational modification of OGG1 significantly augment IFN-λ expression in epithelial cells infected by human respiratory syncytial virus (RSV). Mechanistically, OGG1 bound to 8-oxoGua in proximity to interferon response elements, which inhibits the IRF3/IRF7 and NF-κB/RelA DNA occupancy, while promoting the suppressor NF-κB1/p50-p50 homodimer binding to the IFN-λ2/3 promoter. In a mouse model of bronchiolitis induced by RSV infection, functional ablation of OGG1 by a small molecule inhibitor (TH5487) enhances IFN-λ production, decreases immunopathology, neutrophilia, and confers antiviral protection. These findings suggest that the ROS-generated epigenetic mark 8-oxoGua via its reader OGG1 serves as a homeostatic thresholding factor in IFN-λ expression. Pharmaceutical targeting of OGG1 activity may have clinical utility in modulating antiviral response.
Increased liver stiffness promotes hepatitis B progression by impairing innate immunity in CCl4-induced fibrotic HBV+ transgenic mice
Authors: Bybee Grace , Moeun Youra , Wang Weimin , Kharbanda Kusum K. , Poluektova Larisa Y. , Kidambi Srivatsan , Osna Natalia A. , Ganesan Murali
Published: August 2023

Background

Hepatitis B virus (HBV) infection develops as an acute or chronic liver disease, which progresses from steatosis, hepatitis, and fibrosis to end-stage liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). An increased stromal stiffness accompanies fibrosis in chronic liver diseases and is considered a strong predictor for disease progression. The goal of this study was to establish the mechanisms by which enhanced liver stiffness regulates HBV infectivity in the fibrotic liver tissue.

Methods

For in vitro studies, HBV-transfected HepG2.2.15 cells were cultured on polydimethylsiloxane gels coated by polyelectrolyte multilayer films of 2 kPa (soft) or 24 kPa (stiff) rigidity mimicking the stiffness of the healthy or fibrotic liver. For in vivo studies, hepatic fibrosis was induced in C57Bl/6 parental and HBV+ transgenic (HBVTg) mice by injecting CCl4 twice a week for 6 weeks.

Results

We found higher levels of HBV markers in stiff gel-attached hepatocytes accompanied by up-regulated OPN content in cell supernatants as well as suppression of anti-viral interferon-stimulated genes (ISGs). This indicates that pre-requisite “fibrotic” stiffness increases osteopontin (OPN) content and releases and suppresses anti-viral innate immunity, causing a subsequent rise in HBV markers expression in hepatocytes. In vitro results were corroborated by data from HBVTg mice administered CCl4 (HBVTg CCl4). These mice showed higher HBV RNA, DNA, HBV core antigen (HBcAg), and HBV surface antigen (HBsAg) levels after liver fibrosis induction as judged by a rise in Col1a1, SMA, MMPs, and TIMPs mRNAs and by increased liver stiffness. Importantly, CCl4-induced the pro-fibrotic activation of liver cells, and liver stiffness was higher in HBVTg mice compared with control mice. Elevation of HBV markers and OPN levels corresponded to decreased ISG activation in HBVTg CCl4 mice vs HBVTg control mice.

Conclusion

Based on our data, we conclude that liver stiffness enhances OPN levels to limit anti-viral ISG activation in hepatocytes and promote an increase in HBV infectivity, thereby contributing to end-stage liver disease progression.
Case Report: Cadonilimab-related toxic epidermal necrolysis-like reactions successfully treated with supplemental Adalimumab
Authors: Chen Peng-Yu , Li Zi-Yun , Cai Sui-Qing
Published: August 2023

Cadonilimab is the first bi-specific antibody approved for certain malignancies in June 2022, which has a modified Fc structure to reduce immune-related adverse events. To date, no reports have described Cadonilimab-related toxic epidermal necrolysis (TEN). Here, we report the first case of TEN-like reactions occurring during the treatment of hepatocellular carcinoma with Cadonilimab in combination with Lenvatinib and transarterial chemoembolization, successfully treated with supplemental Adalimumab. We confirmed Cadonilimab as the culprit and observed significant improvement in the patient’s condition following Adalimumab treatment. The case emphasizes the potential risk of Cadonilimab inducing TEN, and suggests that supplemental Adalimumab could be a favorable option for treating refractory Cadonilimab-related TEN.
Impaired thymic iNKT cell differentiation at early precursor stage in murine haploidentical bone marrow transplantation with GvHD
Authors: Zhao Weijia , Wang Yujia , Zhang Xinwei , Hao Jie , Zhang Kunshan , Huang Xiaojun , Chang Yingjun , Wu Hounan , Jin Rong , Ge Qing
Published: August 2023

Introduction

Early recovery of donor-derived invariant natural killer T (iNKT) cells are associated with reduced risk of graft-versus-host disease (GvHD) and overall survival. Patients with severe GvHD, however, had much slower iNKT cell reconstitution relative to conventional T cells.

Methods

To characterize the delay of iNKT cell reconstitution and explore its possible causes, we used a haploidentical bone marrow transplantation (haplo-BMT) mouse model with GvHD. We found the delayed recovery of thymic and peripheral iNKT cell numbers with markedly decreased thymic NKT1 subset in GvHD mice. The defective generation of thymic iNKT precursors with egress capability contributed to the reduced peripheral iNKT cells in GvHD mice. We further identified intermediate NK1.1- NKT1 precursor subpopulations under steady-state conditions and found that the differentiation of these subpopulations was impaired in the thymi of GvHD mice. Detailed characterization of iNKT precursors and thymic microenvironment showed a close association of elevated TCR/co-stimulatory signaling provided by double positive thymocytes and macrophages with defective down-regulation of proliferation, metabolism, and NKT2 signature in iNKT precursor cells. Correspondingly, NKT2 but not NKT1 differentiation was favored in GvHD mice.

Discussion

These data underline the important roles of TCR and co-stimulatory signaling in the differentiation of thymic iNKT subsets under transplantation conditions.
Proinflammatory role of monocytes in SARS-CoV-2 infection in chronic hemodialysis patients
Authors: Bumbea Viorica , Ardelean Luminita , Radulescu Luminita , Damian Luminita , Bumbea Horia , Dumitru Ion , Lambert Claude , Vladareanu Ana-Maria
Published: August 2023

Background

Fully mature monocytes that express CD14, but not CD16, undergo phagocytosis within tissues, whereas non-classical monocytes, CD14-low CD16+, represent <11% of peripheral monocytes and have primary pro-inflammatory functions. Inflammation plays a major role in Covid-19 disease and adds to the inflammation caused by chronic hemodialysis. The aim of our study was to monitor monocyte subsets in five patients with end-stage kidney disease (ESKD) over a 1-year period after a mild Covid-19 infection. Five ESKD patients with a mild Covid-19 infection were monitored using CD14, CD16, CD300e, HLA-DR, CD64, and CD45 panels using a BD FACS Canto flow cytometer.

Results

CD14-low CD16+ was dramatically (p=0,001) decreased in patients during Covid-19 infection, as previously described for patients without chronic renal failure. In addition, CD14-low CD16+ monocytes remained decreased for 10 months after recovery from Covid. Intermediate monocytes increased during Covid-19 infection and decreased 10 months after infection but this subtype of monocytes retained their inflammatory activity with a significant increase in HLA-DR expression after recovery from Covid infection.

Conclusion

Our study shows that ESKD patients had a pro-inflammatory profile induced by Covid 19, but this status was prolonged significantly over a 10-month period. Thus, advanced renal failure treated by hemodialysis did not dramatically change the inflammatory response against to SARS Covid 2. It seems that monocytes retain their inflammatory status for many months in ESKD patients after a Covid-19 infection.
Cycles of heat exposure elevate metabolic enzyme genes and alters digestion in mussels
Authors: Chan Grace , Gracey Andrew Y. , Solares Edwin , Wehrle Beck A. , Connor Kwasi M.
Published: August 2023

The intertidal sea mussel Mytilus californianus inhabits the Pacific coastline of North America. As a sessile organism it must cope with daily fluctuations of the marine and terrestrial environments. Organisms in stressful environments are commonly faced with energetic trade-offs between somatic and reproductive growth and stress management. Although, this energetic theory is generally accepted for mussels as well, the spectrum of mechanisms underlying this framework have not been widely investigated. In the current study we hypothesized that mussels acclimated to a cyclical moderately warm aerial environment would display enhanced transcript abundance of genes related to metabolism and exhibit resilient digestive enzyme activity (energy acquisition). Following acclimation to simulated tidal regimes in the laboratory we observed higher gene-expression of citrate synthase (CS), citrate lyase (ACLY), and mammalian target of rapamycin (MTOR) in heat stressed mussels. The expression of CS and MTOR was not elevated under acute thermal stress, suggestive that repeated stress is required for robust expression of these genes given that all other environmental variables are constant. We also observed reduced activity of the digestive enzyme, amylase in heat-shocked acclimated mussels (a proxy for energy acquisition). Our results suggest that mussels that settle high on shore not only face the challenge of thermal stress repair and limited access to food but may also be compromised by reduced digestive performance. Mussels may have adapted to cyclical energetic stress by overexpressing particular energy-related genes that can mitigate the disturbance to energy balance once the abundant transcripts are translated into functional proteins.
SymmetricNet: end-to-end mesoscale eddy detection with multi-modal data fusion
Authors: Zhao Yuxiao , Fan Zhenlin , Li Haitao , Zhang Rui , Xiang Wei , Wang Shengke , Zhong Guoqiang
Published: August 2023

Mesoscale eddies play a significant role in marine energy and matter transportation. Due to their huge impact on the ocean, mesoscale eddy detection has been studied for many years. However, existing methods mainly use single-modal data, such as the sea surface height (SSH), to detect mesoscale eddies, resulting in inaccurate detection results. In this paper, we propose an end-to-end mesoscale eddy detection method based upon multi-modal data fusion. Particularly, we don’t only use SSH, but also add data of other two modals, i.e., the sea surface temperature (SST) and the velocity of flow, which are closely related to mesoscale eddy detection. Moreover, we design a novel network named SymmetricNet, which is able to achieve multi-modal data fusion in mesoscale eddy detection. The proposed SymmetricNet mainly contains a downsampling pathway and an upsampling pathway, where the low-level feature maps from the downsampling pathway and the high-level feature maps from the upsampling pathway are merged through lateral connections. In addition, we apply dilated convolutions to the network structure to increase the receptive field without sacrificing resolution. Experiments on multi-modal mesoscale eddy dataset demonstrate the advantages of the proposed method over previous approaches for mesoscale eddy detection.
Adsorption of toxic dye using red seaweeds from synthetic aqueous solution and its application to industrial wastewater effluents
Authors: Al-Saeedi Sameerah I. , Ashour Mohamed , Alprol Ahmed E.
Published: August 2023

This study investigated the potential application of dried powder from red seaweedPterocladia capillaceaas an eco-friendly adsorbent for removing Crystal Violet Dye (CV dye) from a synthetic solution. The adsorption conditions for the adsorbent were determined, in batch conditions, by changing different experimental parameters such as initial CV dye concentrations (5, 10, 20, 30, and 40 mg L–1), contact time (15, 30, 60, 120, and 180 min.), adsorbent doses (0.025, 0.05, 0.1, 0.2, and 0.3 g), temperature (25, 35, 45, and 55°C), and pH (3, 5, 7, 9, and 11). The adsorption mechanisms of CV dye onto theP. capillaceabiomass were examined using various analytical techniques such as FTIR, BET, UV–Visible, and SEM. These characterizations suggest the average BET surface area ofP. capillaceawas 87.17 m2g–1and a pore volume of 0.10368 cc g−1. Moreover, according to the FTIR study, the dye has been deposited inside the adsorbent’s pores after adsorption. The adsorption behavior of the adsorbent was investigated by performing both kinetic and equilibrium isothermal studies in batch conditions at 25°C. Also, the thermodynamic factors showed the exothermic nature and physisorption of the adsorption process, which tends to be spontaneous at lower temperatures. In addition, Langmuir, Dubinin-Radushkevich, Freundlich, and Tempkin isotherm models were selected to evaluate the adsorption of CV dye onP. capillacea. The equilibrium adsorption data were best represented by the Freundlich, indicating multilayer adsorption on the heterogeneous surface. The qeexperiment and calculation values for the Pseudo-Second-Order and interparticle diffusion kinetic models were determined. The results showed that, under optimum conditionsP. capillaceaexhibited 98% removal of CV dye from synthetic wastewater. Moreover, it will help to regenerate the adsorbents that can be reused to adsorb CV dye ions and develop a successful adsorption process. Finally, this study concluded that the dried powdered form ofP. capillaceais an attractive source for adsorbing CV dye from aqueous solution.
Microplastic pollution associated with reduced respiration in seagrass (Zostera marina L.) and associated epiphytes
Authors: Molin Jacob Malte , Groth-Andersen William Emil , Hansen Per Juel , Kühl Michael , Brodersen Kasper Elgetti
Published: August 2023

Seagrasses provide crucial ecosystem services of relevance for the marine environment. However, anthropogenic activities are causing global seagrass decline. Increasing microplastic (MP) concentrations have been recognized as a novel threat to many marine organisms, but their effects on marine plants remain underexplored. Here, we investigate the effects of microplastic (polyethylene (PE) and polypropylene (PP)) exposure on the photosynthesis and respiration of the seagrass Zostera marina L. and its associated epiphytes. Measurements were conducted on seagrass leaves with and without epiphyte cover, as well as on epiphytes scraped off the leaf surface. Net gas exchange and pH drift measurements were used to determine rates of photosynthesis and respiration, as well as the ability of leaves and epiphytes to utilize bicarbonate. In addition, variable chlorophyll fluorescence imaging was employed to quantify the photosynthetic capacity of seagrass leaves. Our results show a limited effect of short-term (14 days) microplastic exposure on seagrass leaves and their associated epiphytes, although the photosynthetic activity and respiration rates were gradually reduced for bare seagrass leaves with increasing microplastic concentrations (25-1000 mg MP L-1). A >50% reduction in dark respiration of bare leaves was found at the highest MP exposure, while respiration rates of leaves with epiphytes and separated epiphytes were reduced by maximally ~45 and 30% upon MP exposure, respectively. Short-term microplastic exposure did not alter i) the ability to utilize bicarbonate, ii) the maximum quantum yield of PSII (FV/FM), nor iii) the light utilization efficiency of Z. marina leaves and associated epiphytes. The compensation irradiance decreased for all investigated specimens, and seagrass leaves (with and without epiphytes) were able to retain a positive net oxygen balance throughout all treatments. We speculate that the observed decrease in photosynthetic activity and respiration was caused by leachates from microplastics. Our findings thus indicate that seagrass Z. marina largely possess resilience toward microplastic pollution at its current level.
Transcriptome analysis provides insights into the mechanism of carapace stripe formation in two closely related Marsupenaeus species
Authors: Wang Panpan , Xie Shumin , Li Xinyang , Zhu Jiawei , You Ziqi , Zhou Xinlei , Zhou Xinyi , Yan Binlun , Gao Huan , Xing Chaofan
Published: August 2023

Marsupenaeus japonicus has two types of phenotypic differences that are mainly reflected in the stripe pattern of the carapace. However, the underlying mechanism regulating the stripe patterns is not clear. In the present study, we first observed the composition of pigment cells and detected the contents of different carotenoids in the carapace of M. japonicus. We clearly observed the setae structure on the carapace. There were red pigment cells in the stripe pattern and yellow pigment cells in the other parts. Both red pigment cells and yellow pigment cells showed dendritic morphology. In the carapace, the content of astaxanthin was the highest, significantly (P < 0.05) higher than that of other carotenoids. Some differentially expressed genes between two pattern types of M. japonicus, may be associated with the body color formation, such as crustacyanin (CRCN), apolipoprotein D (ApoD), tubulin alpha-1 chain, cuticle protein, and ABC transporter, which were verified by quantitative PCR experiments. The amino acid composition and secondary structure of CRCN A2, CRCN C1, and ApoD were significantly different. The results of this study will help to elucidate the molecular mechanism of the differential pattern formation of M. japonicus and provide a reference for further exploration of the formation mechanism of crustacean color.
Statistical experiment analysis of wear and mechanical behaviour of abaca/sisal fiber-based hybrid composites under liquid nitrogen environment
Authors: L Natrayan , Surakasi Raviteja , Paramasivam Prabhu , Dhanasekaran Seshathiri , S. Kaliappan , Patil Pravin P.
Published: August 2023

Composite materials are increasingly replacing synthetic fiber combinations in various applications. However, certain extreme environments on Earth and in space require structures to operate under low temperatures, specifically cryogenic conditions, which can significantly affect material reactions. Therefore, the main focus of this study is to develop and evaluate hybridized biocomposites, specifically assessing their tensile, bending, and impact strengths in a controlled liquid nitrogen environment (77 K). Utilizing the Taguchi optimization method, the statistical analysis of wearing characteristics was carried out utilizing cryogenic treatment hours, load, sliding distance, and weight percentage of abaca and sisal fibers. When 20 percent abaca and sisal were mixed, tensile performance increased from 28.96 to 36.58 MPa. Likewise, the same mixture increased bending strength from 59.63 to 75.68 MPa, and impact strength improved from 59.36 to 71.25 J/m. The cryogenic treatment of composite materials for 15–30 min improved the mechanical characteristics of the materials by enhancing the binding between reinforcements and substrate. The Taguchi 27 test outcomes showed a decreased friction coefficient of 7.79 × 105 mm3/Nm in the 10th trial with 30 min of cold working, 10% hybrid fibers, 600 m slide distance, and a 4 N load combination. Frictional coefficient data indicated the lowest rate during the third experiment with 15 min of cryogenic treatment, 10% hybrid fibers, 1,500 m slide length, and a 12 N load combination. The microstructural analysis of the fractured specimen was evaluated by scanning electron microscopy. Finally, such composite materials are employed in liquid propellant tanks, satellites, spaceships, rocket constructions, aeroplane components at cruising altitudes, and other applications.
A new, feasible, and convenient method based on semantic segmentation and deep learning for hemoglobin monitoring
Authors: Hu Xiao-yan , Li Yu-jie , Shu Xin , Song Ai-lin , Liang Hao , Sun Yi-zhu , Wu Xian-feng , Li Yong-shuai , Tan Li-fang , Yang Zhi-yong , Yang Chun-yong , Xu Lin-quan , Chen Yu-wen , Yi Bin
Published: August 2023

Objective

Non-invasive methods for hemoglobin (Hb) monitoring can provide additional and relatively precise information between invasive measurements of Hb to help doctors' decision-making. We aimed to develop a new method for Hb monitoring based on mask R-CNN and MobileNetV3 with eye images as input.

Methods

Surgical patients from our center were enrolled. After image acquisition and pre-processing, the eye images, the manually selected palpebral conjunctiva, and features extracted, respectively, from the two kinds of images were used as inputs. A combination of feature engineering and regression, solely MobileNetV3, and a combination of mask R-CNN and MobileNetV3 were applied for model development. The model's performance was evaluated using metrics such as R2, explained variance score (EVS), and mean absolute error (MAE).

Results

A total of 1,065 original images were analyzed. The model's performance based on the combination of mask R-CNN and MobileNetV3 using the eye images achieved an R2, EVS, and MAE of 0.503 (95% CI, 0.499–0.507), 0.518 (95% CI, 0.515–0.522) and 1.6 g/dL (95% CI, 1.6–1.6 g/dL), which was similar to that based on MobileNetV3 using the manually selected palpebral conjunctiva images (R2: 0.509, EVS:0.516, MAE:1.6 g/dL).

Conclusion

We developed a new and automatic method for Hb monitoring to help medical staffs' decision-making with high efficiency, especially in cases of disaster rescue, casualty transport, and so on.
Mediating effect of gastrointestinal symptoms on dietary behavior and quality of life in Chinese adults with chronic gastritis—a cross-sectional study
Authors: Zhao Litong , Zhang Feng , Kuang Dan , Li Dan , Yan Jiai , Yang Ju , Wang Qinyue , Wang Yingyu , Sun Jing , Liu Yiran , Liu Ping , Xia Yanping , Cao Hong
Published: August 2023

Background

Chronic gastritis is accompanied by varying degrees of gastrointestinal symptoms, which affect people’s quality of life. The association between dietary behaviors and gastrointestinal symptoms of patients with chronic gastritis has been proved recently. However, no studies have been conducted to investigate the relationship between dietary behaviors, gastrointestinal symptoms, and quality of life.

Methods

A cross-sectional survey of 176 patients diagnosed with chronic gastritis aged 18 to 65 years, comprising their information on demographic characteristics, dietary behaviors, gastrointestinal symptoms, and quality of life, was collected. A descriptive analysis and a correlation matrix were used to illuminate the characteristics of the subjects and bivariate correlation, respectively. The mediation model was analyzed using the PROCESS macros for SPSS.

Results

Demographic characteristics were found to influence the symptoms, dietary behaviors, and quality of life of chronic gastritis patients; in particular, students categorized by occupation had higher levels of gastrointestinal symptoms and lower levels of quality of life and dietary behavior. The study variables were all pound related. We found that gastrointestinal symptoms played a partial mediating role between dietary behavior and both the physical components summary and mental components summary, and the ratios of mediating effects to the total effect on the physical components summary and mental components summary were 23.5% and 21.5%, respectively.

Conclusion

Our survey discovered that dietary behavior, gastrointestinal symptoms, and quality of life were all pairwise related. The effect of dietary behavior on quality of life was partially mediated by gastrointestinal symptoms. These results may provide a novel perspective for medical staff in improving the quality of life of patients with chronic gastritis.
Case report: Coxiella burnetii endocarditis in the absence of evident exposure
Authors: Bozza Silvia , Graziani Alessandro , Borghi Monica , Marini Daniele , Duranti Michele , Camilloni Barbara
Published: August 2023

Q fever is a worldwide zoonotic disease caused by Coxiella burnetii. In humans, it can manifest clinically as an acute or chronic disease and endocarditis, the most frequent complication of chronic Q fever is associated with the greatest morbidity and mortality. We report a severe case of endocarditis in a 55-year-old man with a history of aortic valve replacement affected by monoclonal gammopathy of undetermined significance (MGUS), and living in a non-endemic area for C. burnetii. After two episodes of fever of unknown origin (FUO), occurring 2 years apart and characterized by negative blood cultures, a serological diagnosis of Q fever endocarditis was performed even though the patient did not refer to possible past exposure to C. burnetii. Since people with preexisting valvular heart disease, when infected with C. burnetii, have reported a 40% risk of Q fever endocarditis, clinicians should maintain a high index of suspicion for infective endocarditis in all patients with FUO even when the exposure to C. burnetii appears to be unlikely.
Touching the (almost) untouchable: a minimally invasive workflow for microbiological and biomolecular analyses of cultural heritage objects
Authors: Flocco Cecilia G. , Methner Anika , Burkart Franziska , Geppert Alicia , Overmann Jörg
Published: August 2023

Microbiological and biomolecular approaches to cultural heritage research have expanded the established research horizon from the prevalent focus on the cultural objects' conservation and human health protection to the relatively recent applications to provenance inquiry and assessment of environmental impacts in a global context of a changing climate. Standard microbiology and molecular biology methods developed for other materials, specimens, and contexts could, in principle, be applied to cultural heritage research. However, given certain characteristics common to several heritage objects—such as uniqueness, fragility, high value, and restricted access, tailored approaches are required. In addition, samples of heritage objects may yield low microbial biomass, rendering them highly susceptible to cross-contamination. Therefore, dedicated methodology addressing these limitations and operational hurdles is needed. Here, we review the main experimental challenges and propose a standardized workflow to study the microbiome of cultural heritage objects, illustrated by the exploration of bacterial taxa. The methodology was developed targeting the challenging side of the spectrum of cultural heritage objects, such as the delicate written record, while retaining flexibility to adapt and/or upscale it to heritage artifacts of a more robust constitution or larger dimensions. We hope this tailored review and workflow will facilitate the interdisciplinary inquiry and interactions among the cultural heritage research community.
Enhanced probiotic potential of Lactobacillus kefiranofaciens OSU-BDGOA1 through co-culture with Kluyveromyces marxianus bdgo-ym6
Authors: González-Orozco Brianda D. , Kosmerl Erica , Jiménez-Flores Rafael , Alvarez Valente B.
Published: August 2023

Introduction

Due to the increasing consumer demand for the development and improvement of functional foods containing probiotics, new probiotic candidates need to be explored as well as novel means to enhance their beneficial effects. Lactobacillus kefiranofaciens OSU-BDGOA1 is a strain isolated from kefir grains that has demonstrated probiotic traits. This species is the main inhabitant of kefir grains and is responsible for the production of an exopolysaccharide (EPS) whit vast technological applications and potential bioactivities. Research has shown that interkingdom interactions of yeast and lactic acid bacteria can enhance metabolic activities and promote resistance to environmental stressors.

Methods

Comparative genomic analyses were performed to distinguish OSU-BDGOA1 from other strains of the same species, and the genome was mined to provide molecular evidence for relevant probiotic properties. We further assessed the cumulative effect on the probiotic properties of OSU-BDGOA1 and Kluyveromyces marxianus bdgo-ym6 yeast co-culture compared to monocultures.

Results

Survival during simulated digestion assessed by the INFOGEST digestion model showed higher survival of OSU-BDGOA1 and bdgo-ym6 in co-culture. The adhesion to intestinal cells assessed with the Caco-2 intestinal cell model revealed enhanced adhesion of OSU-BDGOA1 in co-culture. The observed increase in survival during digestion could be associated with the increased production of EPS during the late exponential and early stationary phases of co-culture that, by enhancing co-aggregation between the yeast and the bacterium, protects the microorganisms from severe gastrointestinal conditions as observed by SEM images. Immune modulation and barrier function for recovery and prevention of flagellin-mediated inflammation by Salmonella Typhimurium heat-killed cells (HKSC) in Caco-2 cells were also measured. OSU-BDGOA1 in mono- and co-culture regulated inflammation through downregulation of pro-inflammatory cytokine expression and increased membrane barrier integrity assessed by TEER, FD4 permeability, and expression of tight junctions.

Discussion

The results of the study warrant further research into the application of co-cultures of yeast and LAB in functional probiotic products and the potential to increase EPS production by co-culture strategies.
Current and future therapeutic strategies for Alzheimer’s disease: an overview of drug development bottlenecks
Authors: Peng Yong , Jin Hong , Xue Ya-hui , Chen Quan , Yao Shun-yu , Du Miao-qiao , Liu Shu
Published: August 2023

Alzheimer’s disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental symptoms, such as behavioral abnormalities; all of which place a significant psychological and economic burden on the patients’ families. No specific drugs are currently available for the treatment of AD, and the current drugs for AD only delay disease onset and progression. The pathophysiological basis of AD involves abnormal deposition of beta-amyloid protein (Aβ), abnormal tau protein phosphorylation, decreased activity of acetylcholine content, glutamate toxicity, autophagy, inflammatory reactions, mitochondria-targeting, and multi-targets. The US Food and Drug Administration (FDA) has approved five drugs for clinical use: tacrine, donepezil, carbalatine, galantamine, memantine, and lecanemab. We have focused on the newer drugs that have undergone clinical trials, most of which have not been successful as a result of excessive clinical side effects or poor efficacy. Although aducanumab received rapid approval from the FDA on 7 June 2021, its long-term safety and tolerability require further monitoring and confirmation. In this literature review, we aimed to explore the possible pathophysiological mechanisms underlying the occurrence and development of AD. We focused on anti-Aβ and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD.
Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury
Authors: Tozihi Majid , Shademan Behrouz , Yousefi Hadi , Avci Cigir Biray , Nourazarian Alireza , Dehghan Gholamreza
Published: August 2023

Cerebral ischemia-reperfusion (CIR) injury is initiated by the generation of reactive oxygen species (ROS), which leads to the oxidation of cellular proteins, DNA, and lipids as an initial event. The reperfusion process impairs critical cascades that support cell survival, including mitochondrial biogenesis and antioxidant enzyme activity. Failure to activate prosurvival signals may result in increased neuronal cell death and exacerbation of CIR damage. Melatonin, a hormone produced naturally in the body, has high concentrations in both the cerebrospinal fluid and the brain. However, melatonin production declines significantly with age, which may contribute to the development of age-related neurological disorders due to reduced levels. By activating various signaling pathways, melatonin can affect multiple aspects of human health due to its diverse range of activities. Therefore, understanding the underlying intracellular and molecular mechanisms is crucial before investigating the neuroprotective effects of melatonin in cerebral ischemia-reperfusion injury.
A review of brain regions and associated post-concussion symptoms
Authors: Danielli Ethan , Simard Nicholas , DeMatteo Carol A. , Kumbhare Dinesh , Ulmer Stephan , Noseworthy Michael D.
Published: August 2023

The human brain is an exceptionally complex organ that is comprised of billions of neurons. Therefore, when a traumatic event such as a concussion occurs, somatic, cognitive, behavioral, and sleep impairments are the common outcome. Each concussion is unique in the sense that the magnitude of biomechanical forces and the direction, rotation, and source of those forces are different for each concussive event. This helps to explain the unpredictable nature of post-concussion symptoms that can arise and resolve. The purpose of this narrative review is to connect the anatomical location, healthy function, and associated post-concussion symptoms of some major cerebral gray and white matter brain regions and the cerebellum. As a non-exhaustive description of post-concussion symptoms nor comprehensive inclusion of all brain regions, we have aimed to amalgamate the research performed for specific brain regions into a single article to clarify and enhance clinical and research concussion assessment. The current status of concussion diagnosis is highly subjective and primarily based on self-report of symptoms, so this review may be able to provide a connection between brain anatomy and the clinical presentation of concussions to enhance medical imaging assessments. By explaining anatomical relevance in terms of clinical concussion symptom presentation, an increased understanding of concussions may also be achieved to improve concussion recognition and diagnosis.
Diagnosis and therapy of myasthenia gravis—the patients’ perspective: a cross-sectional study
Authors: Sobierajski Tomasz , Lasek-Bal Anetta , Krzystanek Marek , Gilhus Nils E.
Published: August 2023

The survey aimed to explore patients’ perspectives with myasthenia gravis (MG) toward the diagnosis made and the therapy used to treat MG. The survey was conducted with a quantitative method, using the CAWI technique. A total of 321 people participated in the survey. More than half of the respondents (56.4%) had suffered from MG for less than 10 years. In three out of 10 cases (30.9%), the diagnosis of MG lasted 3 years or longer. The diagnostic delay was significantly longer in female respondents than in the males (p = 0.029). Cholinergic drugs were used in 92.9% of cases initially, and as maintenance therapy in 84.3% of cases. Corticosteroids were used in initiating therapy (45.8%) and as maintenance therapy (46.4%). One in four respondents (25.5%) reported experiencing very strong and strong side effects after using steroids. The side effects from steroid therapy very strong or strong affected overall physical health in 55.9% of respondents, very strong or strong affected self-acceptance in 52%, to a very large or large extent on mental health in 47.1%, and to a very strong or strong extent influenced the performance of daily activities in 28.2%. More than half of the respondents (57.0%) had had a thymectomy. Seven out of 10 respondents (72.0%) declared that the therapy they were on at the time of the survey allowed them (to varying degrees) to control their course of MG. Low therapy acceptance and less well controlled MG was associated with a preference for non-tablet therapies (p = 0.045). Regular follow-up and cooperation with the specialist health care system should improve MG symptoms, activities of daily living, and quality of life.
Variation in the rate of recovery in motor function between the upper and lower limbs in patients with stroke: some proposed hypotheses and their implications for research and practice
Authors: Abdullahi Auwal , Wong Thomson W. L. , Ng Shamay S. M.
Published: August 2023

Background

Stroke results in impairment of motor function of both the upper and lower limbs. However, although it is debatable, motor function of the lower limb is believed to recover faster than that of the upper limb. The aim of this paper is to propose some hypotheses to explain the reasons for that, and discuss their implications for research and practice.

Method

We searched PubMED, Web of Science, Scopus, Embase and CENTRAL using the key words, stroke, cerebrovascular accident, upper extremity, lower extremity, and motor recovery for relevant literature.

Result

The search generated a total of 2,551 hits. However, out of this number, 51 duplicates were removed. Following review of the relevant literature, we proposed four hypotheses: natural instinct for walking hypothesis, bipedal locomotion hypothesis, central pattern generators (CPGs) hypothesis and role of spasticity hypothesis on the subject matter.

Conclusion

We opine that, what may eventually account for the difference, is the frequency of use of the affected limb or intensity of the rehabilitation intervention. This is because, from the above hypotheses, the lower limb seems to be used more frequently. When limbs are used frequently, this will result in use-dependent plasticity and eventual recovery. Thus, rehabilitation techniques that involve high repetitive tasks practice such as robotic rehabilitation, Wii gaming and constraint induced movement therapy should be used during upper limb rehabilitation.
Menopausal transition in multiple sclerosis: relationship with disease activity and brain volume measurements
Authors: Lorefice Lorena , Fenu Giuseppe , Fronza Marzia , Murgia Federica , Frau Jessica , Coghe Giancarlo , Barracciu Maria Antonietta , Atzori Luigi , Angioni Stefano , Cocco Eleonora
Published: August 2023

Background

Recent evidence has shown a significant association between menopause and multiple sclerosis (MS) progression. This study investigated the possible role of menopause in influencing MS from clinical and neuroradiological perspectives. Notably, the possible association between menopause and brain atrophy has been evaluated.

Materials and methods

This study included women with MS whose ages ranged from 45 to 55 years. Demographic and clinical characteristics were collected, and the reproductive phase was defined as non-menopausal or menopausal based on the final menstrual period. Thus, MS activity over the past year was reported as the annualised relapse rate (ARR), and MRI activity (defined as new T2 lesions and/or the presence of gadolinium-enhancing lesions at the last MRI assessment in comparison with the MRI performed within the previous 12 months) were compared between non-menopausal women (non-MW) and menopausal women (MW). Volume measurements of the whole brain (WB), white matter (WM), grey matter (GM), and cortical GM were estimated using the SIENAX software, and the possible relationship with menopausal status was assessed by regression analysis.

Results

The study included 147 women with MS. Eighty-four (57.1%) were MW, with a mean age of 48.5 ± 4.3 years at menopause onset and a mean duration of menopause of 4.1 ± 1.1 years. When compared for ARR, MW reported a lower rate than the non-MW (ARR of 0.29 ± 0.4 vs. 0.52 ± 0.5; p < 0.01). MRI activity was observed in 13.1% of MW and 20.6% of non-MW (p = 0.03). Lower cortical GM volumes (578.1 ± 40.4 mL in MW vs. 596.9 ± 35.8 mL in non-MW; p < 0.01) have also been reported. Finally, multivariate analysis showed a significant association of lower ARR (p = 0.001) and cortical GM volume (p = 0.002) with menopausal status after correction for chronological age and other variables.

Discussion

Menopause may be an adverse prognostic factor of MS. Our preliminary results suggest that menopause may facilitate cortical GM atrophy, probably due to a decline in the neuroprotective effects of estrogen, with negative effects on MS evolution.
Associations of air pollution with all-cause dementia, Alzheimer’s disease, and vascular dementia: a prospective cohort study based on 437,932 participants from the UK biobank
Authors: Yuan Shiqi , Huang Xiaxuan , Zhang Luming , Ling Yitong , Tan Shanyuan , Peng Min , Xu Anding , Lyu Jun
Published: August 2023

Objective

To prospectively assess whether air pollution, including PM2.5, PM10, and NOx, is associated with the risk of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia, and to investigate the potential relationship between air pollution and genetic susceptibility in the development of AD.

Methods and results

Our study included 437,932 participants from the UK Biobank with a median follow-up period of over 10 years. Using a Cox proportional hazards model, we found that participants exposed to PM2.5 levels of ≥10 μg/m3 had a higher risk of developing all-cause dementia (HR = 1.1; 95% CI: 1.05–1.28; p < 0.05) compared to the group exposed to PM2.5 levels of <10 μg/m3. However, there was no significant association between PM10 levels of ≥15 μg/m3 and the risk of all-cause dementia, AD, or vascular dementia when compared to the group exposed to PM10 levels of <15 μg/m3. On the other hand, participants exposed to NOx levels of ≥50 μg/m3 had a significantly higher risk of all-cause dementia (HR = 1.14; 95% CI: 1.02–1.26; p < 0.05) and AD (HR = 1.26; 95% CI: 1.08–1.48; p < 0.05) compared to the group exposed to NOx levels of <50 μg/m3. Furthermore, we examined the combined effect of air pollution (PM2.5, PM10, and NOx) and Alzheimer’s disease genetic risk score (AD-GRS) on the development of AD using a Cox proportional hazards model. Among participants with a high AD-GRS, those exposed to NOx levels of ≥50 μg/m3 had a significantly higher risk of AD compared to those in the group exposed to NOx levels of <50 μg/m3 (HR = 1.36; 95% CI: 1.03–1.18; p < 0.05). Regardless of air pollutant levels (PM2.5, PM10, or NOx), participants with a high AD-GRS had a significantly increased risk of developing AD. Similar results were obtained when assessing multiple variables using inverse probability of treatment weighting (IPTW).

Conclusion

Our findings indicate that individuals living in areas with PM2.5 levels of ≥10 μg/m3 or NOx levels of ≥50 μg/m3 are at a higher risk of developing all-cause dementia. Moreover, individuals with a high AD-GRS demonstrated an increased risk of developing AD, particularly in the presence of NOx ≥ 50 μg/m3.
The gut microbiota–brain axis in neurological disorder
Authors: Ullah Hanif , Arbab Safia , Tian Yali , Liu Chang-qing , Chen Yuwen , Qijie Li , Khan Muhammad Inayat Ullah , Hassan Inam Ul , Li Ka
Published: August 2023

The gut microbiota (GM) plays an important role in the physiology and pathology of the host. Microbiota communicate with different organs of the organism by synthesizing hormones and regulating body activity. The interaction of the central nervous system (CNS) and gut signaling pathways includes chemical, neural immune and endocrine routes. Alteration or dysbiosis in the gut microbiota leads to different gastrointestinal tract disorders that ultimately impact host physiology because of the abnormal microbial metabolites that stimulate and trigger different physiologic reactions in the host body. Intestinal dysbiosis leads to a change in the bidirectional relationship between the CNS and GM, which is linked to the pathogenesis of neurodevelopmental and neurological disorders. Increasing preclinical and clinical studies/evidence indicate that gut microbes are a possible susceptibility factor for the progression of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and autism spectrum disorder (ASD). In this review, we discuss the crucial connection between the gut microbiota and the central nervous system, the signaling pathways of multiple biological systems and the contribution of gut microbiota-related neurological disorders.
TUBB3 and KIF21A in neurodevelopment and disease
Authors: Puri Dharmendra , Barry Brenda J. , Engle Elizabeth C.
Published: August 2023

Neuronal migration and axon growth and guidance require precise control of microtubule dynamics and microtubule-based cargo transport. TUBB3 encodes the neuronal-specific β-tubulin isotype III, TUBB3, a component of neuronal microtubules expressed throughout the life of central and peripheral neurons. Human pathogenic TUBB3 missense variants result in altered TUBB3 function and cause errors either in the growth and guidance of cranial and, to a lesser extent, central axons, or in cortical neuronal migration and organization, and rarely in both. Moreover, human pathogenic missense variants in KIF21A, which encodes an anterograde kinesin motor protein that interacts directly with microtubules, alter KIF21A function and cause errors in cranial axon growth and guidance that can phenocopy TUBB3 variants. Here, we review reported TUBB3 and KIF21A variants, resulting phenotypes, and corresponding functional studies of both wildtype and mutant proteins. We summarize the evidence that, in vitro and in mouse models, loss-of-function and missense variants can alter microtubule dynamics and microtubule-kinesin interactions. Lastly, we highlight additional studies that might contribute to our understanding of the relationship between specific tubulin isotypes and specific kinesin motor proteins in health and disease.
Touch may reduce cognitive load during assisted typing by individuals with developmental disabilities
Authors: Nicoli Giovanni , Pavon Giulia , Grayson Andrew , Emerson Anne , Mitra Suvobrata
Published: August 2023

Many techniques have attempted to provide physical support to ease the execution of a typing task by individuals with developmental disabilities (DD). These techniques have been controversial due to concerns that the support provider’s touch can influence the typed content. The most common interpretation of assisted typing as an ideomotor phenomenon has been qualified recently by studies showing that users with DD make identifiable contributions to the process. This paper suggests a neurophysiological pathway by which touch could lower the cognitive load of seated typing by people with DD. The required sensorimotor processes (stabilizing posture and planning and executing manual reaching movements) and cognitive operations (generating and transcribing linguistic material) place concurrent demands on cognitive resources, particularly executive function (EF). A range of developmental disabilities are characterized by deficits in sensorimotor and EF capacity. As light touch has been shown to facilitate postural coordination, it is proposed that a facilitator’s touch could assist the seated typist with sensorimotor and EF deficits by reducing their sensorimotor workload and thereby freeing up shared cognitive resources for the linguistic elements of the task. This is the first theoretical framework for understanding how a facilitator’s touch may assist individuals with DD to contribute linguistic content during touch-assisted typing.