bluuebunny/crossref_metadata_2025 huggingface dataset:
Reforming International Fisheries Law Can Increase Blue Carbon Sequestration
Authors: Krabbe Niels , Langlet David , Belgrano Andrea , Villasante Sebastian
Published: April 2022

The oceans are by far the largest carbon sink and are estimated to have absorbed roughly 40 percent of anthropogenic carbon dioxide emissions since the beginning of the industrial era. The climate services performed by the oceans can be described as an interaction between a physical and a biological carbon pump. Whereas the role of the physical carbon pump is well established, the full scale of the climate services provided by the biological carbon pump has only recently been understood. This pump is made up of services provided by different marine species, from microbes to marine mammals. Many of these species are managed under the international law of the sea and subject to the concept of Maximum Sustainable Yield (MSY). Although the MSY concept has developed since its inception, maximum generation of fish for human consumption remains the core objective according to the law of the sea. Under MSY based management, states are not required to consider the climate services represented by different marine organisms, making this regime unable to balance the interest of maximizing fish as a product against the oceans’ role in carbon sequestration. In order to make optimal use of the carbon sequestering features of marine organisms, this perspective proposes five action points. Foremost, MSY should be complemented with a new management objective: maximum carbon sequestration (MCS). Although many aspects of climate-based fisheries management remain to be explored, it appears clear that this would imply allowing stocks to recover to maintain a larger amount of biomass, increasing conservation measures for species particularly efficient in providing negative emissions, differentiation of fisheries within species as well as a new approach to ecosystem management. Climate reforming international fisheries law could make an important contribution to the operationalization of the Paris Agreement on Climate Change, as well as the UN Sustainable Development Goals. As a first step, international guidelines should be developed on how to integrate the concept of maximum carbon sequestration in fisheries management.
Numerical Modeling and Experimental Validation of TiC Nanoparticle Distribution During the Ultrasonic Casting Process of 2219 Aluminum Matrix Nanocomposites
Authors: Yi-Long Yang , Yun Zhang , Hao-Ming Zhang , Xu-He Liu
Published: April 2022

In this work, a two-dimensional model of 0.9 wt% TiC nanoparticle-reinforced 2219 aluminum nanocomposites fabricated by a high-intensity ultrasonic casting technique was established. The TiC nanoparticle distribution in 2219 aluminum melts was investigated using the multiphase computational fluid dynamics ultrasonic cavitation model accounting for turbulent flow. And the variable interaction between nanoparticles and melts was analyzed by Ansys’s Fluent Dense Discrete phase Model According to the simulation results, the ultrasonic power had a significant effect on the distribution of TiC nanoparticles in aluminum melt. The appropriate ultrasonic power has a promoting effect on the dispersion of nanoparticles. Due to the impact of ultrasonic streaming, the number of nanoparticles in the center position was lower than that in the edge position of the molten pool. Moreover, casting experiments were carried out to verify the efficacy and accuracy of the simulation. The average grain size in the center position was smaller than that in the edge position. TEM and SEM were used to analyze the distribution of TiC nanoparticles. They were more evenly distributed in the center position of the ingot than those in the edge part. Besides more nanoparticles were agglomerated in the edge. The experimental results were mostly consistent with the simulation results.
Case Report: Botulinum Toxin-A for Complication of Exposure Keratopathy Following Frontalis-Orbicularis Oculi Muscle Flap Shortening
Authors: Lai Chun-Chieh , Lin Chia-Chen
Published: April 2022

Background

Lagophthalmos with exposure keratopathy is a potential vision-threatening complication following surgery for blepharoptosis. We report three cases successfully treated with botulinum toxin-A (Botox®, Allergan, Irvine, USA) for this complication.

Cases

Three patients presented with severe blepharoptosis after surgery for orbital and frontal base tumors. They obtained good appearances after frontalis-orbicularis oculi muscle (FOOM) flap shortening. However, exposure keratopathy developed after the surgery despite frequent use of topical lubricants and autologous serum eye drops. We injected 5-10 units of botulinum toxin-A around the central supra-brow area, which was near the origin of the FOOM flap. One week later, they developed ptosis and could close the eye completely. The corneal defect gradually resolved. They recovered from ptosis 3 months later and never required a second injection.

Observations

Lagophthalmos with exposure keratopathy is a potential vision-threatening complication following FOOM flap surgery. In severe cases, surgical revision should be considered to partially or totally release the FOOM flap attachment, which also decreases its function permanently. In this case series, we demonstrated that injecting botulinum toxin-A may be a promising method to manage this complication without permanently affecting the function of the FOOM flap.

Conclusions

A botulinum toxin-A injection may be an effective treatment for patients developing exposure keratopathy after FOOM flap surgery.
Epigenetic Modification: A Key Tool for Secondary Metabolite Production in Microorganisms
Authors: Bind Sudha , Bind Sandhya , Sharma A. K. , Chaturvedi Preeti
Published: April 2022

Microorganisms are stupendous source of secondary metabolites, having significant pharmaceutical and industrial importance. Genome mining has led to the detection of several cryptic metabolic pathways in the natural producer of secondary metabolites (SMs) such as actinobacteria and fungi. Production of these bioactive compounds in considerable amount is, however, somewhat challenging. This led to the search of using epigenetics as a key mechanism to alter the expression of genes that encode the SMs toward higher production in microorganisms. Epigenetics is defined as any heritable change without involving the changes in the underlying DNA sequences. Epigenetic modifications include chromatin remodeling by histone posttranslational modifications, DNA methylation, and RNA interference. Biosynthetic gene cluster for SMs remains in heterochromatin state in which the transcription of constitutive gene is regulated by epigenetic modification. Therefore, small-molecule epigenetic modifiers, which promote changes in the structure of chromatin, could control the expression of silent genes and may be rationally employed for discovery of novel bioactive compounds. This review article focuses on the types of epigenetic modifications and their impact on gene expression for enhancement of SM production in microorganisms.
Differential Detection of Bioavailable Mercury and Cadmium Based on a Robust Dual-Sensing Bacterial Biosensor
Authors: Hui Chang-ye , Guo Yan , Li Han , Chen Yu-ting , Yi Juan
Published: April 2022

Genetically programmed biosensors have been widely used to monitor bioavailable heavy metal pollutions in terms of their toxicity to living organisms. Most bacterial biosensors were initially designed to detect specific heavy metals such as mercury and cadmium. However, most available biosensors failed to distinguish cadmium from various heavy metals, especially mercury. Integrating diverse sensing elements into a single genetic construct or a single host strain has been demonstrated to quantify several heavy metals simultaneously. In this study, a dual-sensing construct was assembled by employing mercury-responsive regulator (MerR) and cadmium-responsive regulator (CadR) as the separate sensory elements and enhanced fluorescent protein (eGFP) and mCherry red fluorescent protein (mCherry) as the separate reporters. Compared with two corresponding single-sensing bacterial sensors, the dual-sensing bacterial sensor emitted differential double-color fluorescence upon exposure to 0–40 μM toxic Hg(II) and red fluorescence upon exposure to toxic Cd(II) below 200 μM. Bioavailable Hg(II) could be quantitatively determined using double-color fluorescence within a narrow concentration range (0–5 μM). But bioavailable Cd(II) could be quantitatively measured using red fluorescence over a wide concentration range (0–200 μM). The dual-sensing biosensor was applied to detect bioavailable Hg(II) and Cd(II) simultaneously. Significant higher red fluorescence reflected the predominant pollution of Cd(II), and significant higher green fluorescence suggested the predominant pollution of Hg(II). Our findings show that the synergistic application of various sensory modules contributes to an efficient biological device that responds to concurrent heavy metal pollutants in the environment.
Trends of Transmitted and Acquired Drug Resistance in Europe From 1981 to 2019: A Comparison Between the Populations of Late Presenters and Non-late Presenters
Authors: Miranda Mafalda N. S. , Pingarilho Marta , Pimentel Victor , Martins Maria do Rosário O. , Kaiser Rolf , Seguin-Devaux Carole , Paredes Roger , Zazzi Maurizio , Incardona Francesca , Abecasis Ana B.
Published: April 2022

Background

The increased use of antiretroviral therapy (ART) has decreased mortality and morbidity of HIV-1 infected people but increasing levels of HIV drug resistance threatens the success of ART regimens. Conversely, late presentation can impact treatment outcomes, health costs, and potential transmission of HIV.

Objective

To describe the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in HIV-1 infected patients followed in Europe, to compare its patterns in late presenters (LP) vs non-late presenters (NLP), and to analyze the most prevalent drug resistance mutations among HIV-1 subtypes.

Methods

Our study included clinical, socio-demographic, and genotypic information from 26,973 HIV-1 infected patients from the EuResist Integrated Database (EIDB) between 1981 and 2019.

Results

Among the 26,973 HIV-1 infected patients in the analysis, 11,581 (42.9%) were ART-naïve patients and 15,392 (57.1%) were ART-experienced. The median age was 37 (IQR: 27.0–45.0) years old and 72.6% were males. The main transmission route was through heterosexual contact (34.9%) and 81.7% of patients originated from Western Europe. 71.9% of patients were infected by subtype B and 54.8% of patients were classified as LP. The overall prevalence of TDR was 12.8% and presented an overall decreasing trend (p for trend < 0.001), the ADR prevalence was 68.5% also with a decreasing trend (p for trend < 0.001). For LP and NLP, the TDR prevalence was 12.3 and 12.6%, respectively, while for ADR, 69.9 and 68.2%, respectively. The most prevalent TDR drug resistance mutations, in both LP and NLP, were K103N/S, T215rev, T215FY, M184I/V, M41I/L, M46I/L, and L90M.

Conclusion

Our study showed that the overall TDR (12.8%) and ADR (68.5%) presented decreasing trends during the study time period. For LP, the overall TDR was slightly lower than for NLP (12.3 vs 12.6%, respectively); while this pattern was opposite for ADR (LP slightly higher than NLP). We suggest that these differences, in the case of TDR, can be related to the dynamics of fixation of drug resistance mutations; and in the case of ADR with the more frequent therapeutic failure in LPs.
LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation
Authors: Yang Yongheng , Li Mengyun , Ma Yongtao , Ye Wei , Si Yue , Zheng Xuyang , Liu He , Cheng Linfeng , Zhang Liang , Zhang Hui , Zhang Xijing , Lei Yingfeng , Shen Lixin , Zhang Fanglin , Ma Hongwei
Published: April 2022

As the global prototypical zoonotic hantavirus, Hantaan virus (HTNV) is prevalent in Asia and is the leading causative agent of severe hemorrhagic fever with renal syndrome (HFRS), which has profound morbidity and mortality. Macrophages are crucial components of the host innate immune system and serve as the first line of defense against HTNV infection. Previous studies indicated that the viral replication efficiency in macrophages determines hantavirus pathogenicity, but it remains unknown which factor manipulates the macrophage activation pattern and the virus-host interaction process. Here, we performed the transcriptomic analysis of HTNV-infected mouse bone marrow-derived macrophages and identified the long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1), especially the isoform NEAT1-2, as one of the lncRNAs that is differentially expressed at the early phase. Based on coculture experiments, we revealed that silencing NEAT1-2 hinders inflammatory macrophage activation and facilitates HTNV propagation, while enhancing NEAT1-2 transcription effectively restrains viral replication. Furthermore, sterol response element binding factor-2 (SREBP2), which controls the cholesterol metabolism process, was found to stimulate macrophages by promoting the production of multiple inflammatory cytokines upon HTNV infection. NEAT1-2 could potentiate SREBP2 activity by upregulating Srebf1 expression and interacting with SREBP2, thus stimulating inflammatory macrophages and limiting HTNV propagation. More importantly, we demonstrated that the NEAT1-2 expression level in patient monocytes was negatively correlated with viral load and HFRS disease progression. Our results identified a function and mechanism of action for the lncRNA NEAT1 in heightening SREBP2-mediated macrophage activation to restrain hantaviral propagation and revealed the association of NEAT1 with HFRS severity.
Adhesion and Colonization of the Probiotic Lactobacillus plantarum HC-2 in the Intestine of Litopenaeus Vannamei Are Associated With Bacterial Surface Proteins
Authors: Du Yang , Li Hao , Shao Jianchun , Wu Ting , Xu WenLong , Hu Xiaoman , Chen Jiong
Published: April 2022

Surface proteins are a type of proteins expressed on the surface of bacteria that play an important role in cell wall synthesis, maintenance of cell morphology, and signaling with the host. Our previous study showed that the probiotic Lactobacillus plantarum HC-2 improved the growth performance and immune response of Litopenaeus vannamei. To further investigate the probiotic mechanism, we determined the automatic aggregation ability of the bacteria and surface hydrophobicity of HC-2 after being treated with 5 M of lithium chloride (LiCl) and observed the morphology and adhesion of the bacteria to HCT116 cells. The results showed that with the removal of the HC-2 surface protein, the auto-aggregation ability and surface hydrophobicity of HC-2 decreased, and the crude mucus layer coated on the bacterial surface gradually dissociated. The adhesion rate of HC-2 to HCT116 cells decreased from 98.1 to 20.9%. Moreover, a total of 201 unique proteins were identified from the mixture of the surface proteins by mass spectrometry (MS). Several proteins are involved in transcription and translation, biosynthetic or metabolic process, cell cycle or division, cell wall synthesis, and emergency response. Meanwhile, a quantitative real-time PCR qPCR_ showed that HC-2 was mainly colonized in the midgut of shrimp, and the colonization numbers were 15 times higher than that in the foregut, while the colonization rate in the hindgut was lower. The adhesion activity measurement showed that the adhesion level of HC-2 to crude intestinal mucus of L. vannamei was higher than that of bovine serum albumin (BSA) and collagen, and the adhesion capacity of the bacterial cells decreased with the extension of LiCl-treatment time. Finally, we identified the elongation factor Tu, Type I glyceraldehyde-3-phosphate dehydrogenase, small heat shock protein, and 30S ribosomal protein from the surface proteins, which may be the adhesion proteins of HC-2 colonization in the shrimp intestine. The above results indicate that surface proteins play an important role in maintaining the cell structure stability and cell adhesion. Surface proteomics analysis contributes to describing potential protein-mediated probiotic-host interactions. The identification of some interacting proteins in this work may be beneficial to further understand the adhesion/colonization mechanism and probiotic properties of L. plantarum HC-2 in the shrimp intestine.
Unifying Single-Channel Permeability From Rare-Event Sampling and Steady-State Flux
Authors: Lin Yi-Chun , Luo Yun Lyna
Published: April 2022

Various all-atom molecular dynamics (MD) simulation methods have been developed to compute free energies and crossing rates of ions and small molecules through ion channels. However, a systemic comparison across different methods is scarce. Using a carbon nanotube as a model of small conductance ion channel, we computed the single-channel permeability for potassium ion using umbrella sampling, Markovian milestoning, and steady-state flux under applied voltage. We show that a slightly modified inhomogeneous solubility-diffusion equation yields a single-channel permeability consistent with the mean first passage time (MFPT) based method. For milestoning, applying cylindrical and spherical bulk boundary conditions yield consistent MFPT if factoring in the effective bulk concentration. The sensitivity of the MFPT to the output frequency of collective variables is highlighted using the convergence and symmetricity of the inward and outward MFPT profiles. The consistent transport kinetic results from all three methods demonstrated the robustness of MD-based methods in computing ion channel permeation. The advantages and disadvantages of each technique are discussed, focusing on the future applications of milestoning in more complex systems.
Function and Therapeutic Implications of tRNA Derived Small RNAs
Authors: Wilson Briana , Dutta Anindya
Published: April 2022

tRNA derived small RNAs are mainly composed of tRNA fragments (tRFs) and tRNA halves (tiRs). Several functions have been attributed to tRFs and tiRs since their initial characterizations, spanning all aspects of regulation of the Central Dogma: from nascent RNA silencing, to post-transcriptional gene silencing, and finally, to translational regulation. The length distribution, sequence diversity, and multifaceted functions of tRFs and tiRs positions them as attractive new models for small RNA therapeutics. In this review, we will discuss the principles of tRF biogenesis and function in order to highlight their therapeutic potential.
Higher Grade Glioma Increases the Risk of Postoperative Delirium: Deficient Brain Compensation Might Be a Potential Mechanism of Postoperative Delirium
Authors: Huang Hua-Wei , Zhang Xiao-Kang , Li Hao-Yi , Wang Yong-Gang , Jing Bin , Chen You , Patel Mayur B. , Ely E. Wesley , Liu Ya-Ou , Zhou Jian-Xin , Lin Song , Zhang Guo-Bin
Published: April 2022

Objective

The brain compensation mechanism in postoperative delirium (POD) has not been reported. We uncovered the mechanism by exploring the association between POD and glioma grades, and the relationship between preoperative brain structural and functional compensation with POD in patients with frontal glioma.

Methods

A total of 335 adult patients with glioma were included. The multivariable analysis examined the association between tumor grade and POD. Then, 20 patients with left frontal lobe glioma who had presurgical structural and functional MRI data and Montreal Cognitive Assessment (MoCA) in this cohort were analyzed. We measured the gray matter volume (GMV) and functional connectivity (FC) in patients with (n = 8) and without (n = 12) POD and healthy controls (HCs, n = 29) to detect the correlation between the structural and functional alteration and POD.

Results

The incidence of POD was 37.3%. Multivariable regression revealed that high-grade glioma had approximately six times the odds of POD. Neuroimaging data showed that compared with HC, the patients with left frontal lobe glioma showed significantly increased GMV of the right dorsal lateral prefrontal cortex (DLPFC) in the non-POD group and decreased GMV of right DLPFC in the POD group, and the POD group exhibited significantly decreased FC of right DLPFC, and the non-POD group showed the increasing tendency. Partial correlation analysis showed that GMV in contralesional DLPFC were positively correlated with preoperative neurocognition, and the GMV and FC in contralesional DLPFC were negatively correlated with POD.

Conclusions

Our findings suggested that insufficient compensation for injured brain regions involving cognition might be more vulnerable to suffering from POD.
Bio-Receptors Functionalized Nanoparticles: A Resourceful Sensing and Colorimetric Detection Tool for Pathogenic Bacteria and Microbial Biomolecules
Authors: Daramola Oluwafemi B. , Omole Richard K. , Akinwale Ifeoluwa V. , Otuyelu Frank O. , Akinsanola Bolanle A. , Fadare Taiwo O. , George Reama C. , Torimiro Nkem
Published: April 2022

Pathogenic bacteria and several biomolecules produced by cells and living organisms are common biological components posing a harmful threat to global health. Several studies have devised methods for the detection of varying pathogenic bacteria and biomolecules in different settings such as food, water, soil, among others. Some of the detection studies highlighting target pathogenic bacteria and biomolecules, mechanisms of detection, colorimetric outputs, and detection limits have been summarized in this review. In the last 2 decades, studies have harnessed various nanotechnology-based methods for the detection of pathogenic bacteria and biomolecules with much attention on functionalization techniques. This review considers the detection mechanisms, colorimetric prowess of bio-receptors and compares the reported detection efficiency for some bio-receptor functionalized nanoparticles. Some studies reported visual, rapid, and high-intensity colorimetric detection of pathogenic bacteria and biomolecules at a very low concentration of the analyte. Other studies reported slight colorimetric detection only with a large concentration of an analyte. The effectiveness of bio-receptor functionalized nanoparticles as detection component varies depending on their selectivity, specificity, and the binding interaction exhibited by nanoparticles, bio-receptor, and analytes to form a bio-sensing complex. It is however important to note that the colorimetric properties of some bio-receptor functionalized nanoparticles have shown strong and brilliant potential for real-time and visual-aided diagnostic results, not only to assess food and water quality but also for environmental monitoring of pathogenic bacteria and a wide array of biomolecules.
Optical Ultrastructure of Large Mammalian Hearts Recovers Discordant Alternans by In Silico Data Assimilation
Authors: Loppini Alessandro , Erhardt Julia , Fenton Flavio H. , Filippi Simonetta , Hörning Marcel , Gizzi Alessio
Published: April 2022

Understanding and predicting the mechanisms promoting the onset and sustainability of cardiac arrhythmias represent a primary concern in the scientific and medical communities still today. Despite the long-lasting effort in clinical and physico-mathematical research, a critical aspect to be fully characterized and unveiled is represented by spatiotemporal alternans patterns of cardiac excitation. The identification of discordant alternans and higher-order alternating rhythms by advanced data analyses as well as their prediction by reliable mathematical models represents a major avenue of research for a broad and multidisciplinary scientific community. Current limitations concern two primary aspects: 1) robust and general-purpose feature extraction techniques and 2) in silico data assimilation within reliable and predictive mathematical models. Here, we address both aspects. At first, we extend our previous works on Fourier transformation imaging (FFI), applying the technique to whole-ventricle fluorescence optical mapping. Overall, we identify complex spatial patterns of voltage alternans and characterize higher-order rhythms by a frequency-series analysis. Then, we integrate the optical ultrastructure obtained by FFI analysis within a fine-tuned electrophysiological mathematical model of the cardiac action potential. We build up a novel data assimilation procedure demonstrating its reliability in reproducing complex alternans patterns in two-dimensional computational domains. Finally, we prove that the FFI approach applied to both experimental and simulated signals recovers the same information, thus closing the loop between the experiment, data analysis, and numerical simulations.
Anterior Circulation Acute Ischemic Stroke in the Plateau of China: Risk Factors and Clinical Characteristics
Authors: Yan Yujia , Zhang Xiqiang , Ren Hecheng , An Xingwei , Fan Wanpeng , Liang Jingbo , Huang Ying
Published: April 2022

Background and Purpose

Acute ischemic stroke has a high incidence in the plateau of China. It has unique characteristics compared to the plains, and the specific relationship with altitude has not yet been appreciated. This study aimed to investigate the specificity of the plateau's anterior circulation acute ischemic stroke in China.

Methods

To retrospectively collect clinical data of patients with first-episode acute ischemic stroke in the anterior circulation in Tianjin and Xining city. The differences in clinical presentation, laboratory, and imaging examinations were compared.

Results

Patients at high altitudes showed a significant trend toward lower age (61.0 ± 10.2 vs. 64.8 ± 8.1, P = 0.010) and had a history of dyslipidemia, higher levels of inflammatory markers, erythrocytosis, and alcohol abuse. The main manifestations were higher diastolic blood pressure (85.5 ± 14.0 mmHg vs. 76.8 ± 11.6 mmHg, P < 0.001), triglycerides [2.0 (1.8) mmol/L vs. 1.3 (0.9) mmol/L, P < 0.001], CRP [4.7 (4.4) mg/L vs. 2.1 (1.9) mg/L, P < 0.001], homocysteine levels [14.5 (11.7) μmol/L vs. 11.2 (5.2) μmol/L, P < 0.001]; larger infarct volume [3.5 (4.8) cm3 vs. 9.0 (6.9) cm3, P < 0.001] and worse prognosis. Patients at high altitudes had higher atherosclerotic indexes in cIMT and plaque than those in plains.

Conclusions

The natural habituation and genetic adaptation of people to the particular geo-climatic environment of the plateau have resulted in significant differences in disease characteristics. Patients with the anterior circulation acute ischemic stroke in the plateau show more unfavorable clinical manifestations and prognosis. This study provides a preliminary interpretation of the effects of altitude and suggests developing preventive and therapeutic protocol measures that are more appropriate for the plateau of China.
Study of Geometric Illusory Visual Perception – A New Perspective in the Functional Evaluation of Children With Strabismus
Authors: Rohr Juliana Tessari Dias , Isaac Cassiano Rodrigues , de Lima Adriano de Almeida , Garcia Ana , dos Santos Procópio Miguel , Tavares Maria Clotilde Henriques
Published: April 2022

Despite the various perceptual-motor deficits documented in strabismus, there is a paucity of studies evaluating visual illusions in patients with strabismus. The aim of this study was to examine how the illusionary perception occurs in children/adolescents (10–15 years old) with strabismus with referral for surgery to correct ocular deviations. A controlled cross-sectional study was carried out in which 45 participants with strabismus and 62 healthy volunteers aged 10–15 years were evaluated. The behavioral response to three geometric illusions [Vertical-Horizontal illusion, Müller-Lyer illusion (Bretano version) and Ponzo illusion] and respective neutral stimuli (non-illusory images) regarding the estimation of image size and response time were measured using the Method of Adjustment. To analyze the influence of secondary factors: type of ocular deviation (convergent, divergent or associated with vertical deviation); amount of eye deviation; presence of amblyopia and stereopsis, a one-way ANOVA was performed. Among the tested illusions, children with strabismus showed greater susceptibility (p = 0.006) and response time (p = 0.004) to Ponzo’s illusory images. Children with strabismus and preserved stereopsis, on the other hand, showed similar susceptibility and response time to control group patients to the Ponzo illusion (p < 0.005). Patients with amblyopia showed overcorrection in the estimate of non-illusory Ponzo images (p = 0.046). Children with horizontal ocular deviation (esotropia or exotropia) associated with vertical deviation (hypertropia, DVD and/or alphabetical anisotropy) showed higher susceptibility to vertical adjustment images for the Müller-Lyer illusion (Brentano version) (p = 0.017). Individuals with strabismus tended to overcorrect the length of the straight-line segment adjusted for non-illusory images when testing non-illusory images in the Müller-Lyer test (Brentano version) (p = 0.009), as well as for the neutral images in the Vertical-Horizontal test (p = 0.000). The findings indicated impairment in the perception of geometric illusions and neutral figures, especially for the Ponzo illusion test by children with strabismus. As the behavioral response to illusory images may indirectly reflect the visual and morphofunctional alterations present in these individuals, we suggest that the investigation of visual illusory perception can be used as a new research strategy in the field of investigating the visual function in strabismus.
A Graph Fourier Transform Based Bidirectional Long Short-Term Memory Neural Network for Electrophysiological Source Imaging
Authors: Jiao Meng , Wan Guihong , Guo Yaxin , Wang Dongqing , Liu Hang , Xiang Jing , Liu Feng
Published: April 2022

Electrophysiological source imaging (ESI) refers to the process of reconstructing underlying activated sources on the cortex given the brain signal measured by Electroencephalography (EEG) or Magnetoencephalography (MEG). Due to the ill-posed nature of ESI, solving ESI requires the design of neurophysiologically plausible regularization or priors to guarantee a unique solution. Recovering focally extended sources is more challenging, and traditionally uses a total variation regularization to promote spatial continuity of the activated sources. In this paper, we propose to use graph Fourier transform (GFT) based bidirectional long-short term memory (BiLSTM) neural network to solve the ESI problem. The GFT delineates the 3D source space into spatially high, medium and low frequency subspaces spanned by corresponding eigenvectors. The low frequency components can naturally serve as a spatially low-band pass filter to reconstruct extended areas of source activation. The BiLSTM is adopted to learn the mapping relationship between the projection of low-frequency graph space and the recorded EEG. Numerical results show the proposed GFT-BiLSTM outperforms other benchmark algorithms in synthetic data under varied signal-to-noise ratios (SNRs). Real data experiments also demonstrate its capability of localizing the epileptogenic zone of epilepsy patients with good accuracy.
Auditory Dysfunction in Animal Models of Autism Spectrum Disorder
Authors: Castro Ana Carolina , Monteiro Patricia
Published: April 2022

Autism spectrum disorder (ASD) is a neurodevelopmental disorder mainly characterized by social-communication impairments, repetitive behaviors and altered sensory perception. Auditory hypersensitivity is the most common sensory-perceptual abnormality in ASD, however, its underlying neurobiological mechanisms remain elusive. Consistently with reports in ASD patients, animal models for ASD present sensory-perception alterations, including auditory processing impairments. Here we review the current knowledge regarding auditory dysfunction in rodent models of ASD, exploring both shared and distinct features among them, mechanistic and molecular underpinnings, and potential therapeutic approaches. Overall, auditory dysfunction in ASD models seems to arise from impaired central processing. Depending on the model, impairments may arise at different steps along the auditory pathway, from auditory brainstem up to the auditory cortex. Common defects found across models encompass atypical tonotopicity in different regions of the auditory pathway, temporal and spectral processing impairments and histological differences. Imbalance between excitation and inhibition (E/I imbalance) is one of the most well-supported mechanisms explaining the auditory phenotype in the ASD models studied so far and seems to be linked to alterations in GABAergic signaling. Such E/I imbalance may have a large impact on the development of the auditory pathway, influencing the establishment of connections responsible for normal sound processing.
Modulating Effect of Paeonol on Piglets With Ulcerative Colitis
Authors: Wang Shanshan , Bai Miaomiao , Shu Qingyan , Liu Zhengan , Shao Yirui , Xu Kang , Xiong Xia , Liu Hongnan , Li Yao
Published: April 2022

Piglet enteritis is a major problem that needs to be solved urgently in modern pig production. Paeonol (Pae) has been used as a novel treatment option due to its good medicinal value. This study purported to elucidate the regulatory mechanism of Pae on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in weaned piglets. A total of 36 crossbred (Duroc × Landrace × Yorkshire) weaned piglets were stochastically split into six groups: the control group, DSS group, 0.2% Pae group, 0.4% Pae group, 0.8% Pae group, and mesalazine group. The control and DSS groups were fed with a basic diet, the three Pae and mesalazine groups were fed with 0.2, 0.4, 0.8%, and 2 g mesalazine per kilogram of basic diet throughout the study. On the 15th day of the test period, the control group was gavaged with 10 ml of normal saline, while the remaining five groups were gavaged with 10 ml 5% DSS solution for 13 days. The study lasted for 27 days. The results showed that the 0.8% Pae group significantly increased the average daily feed intake (ADFI) and Occludin mRNA expression in the colon of piglets (P < 0.05). The 0.2% Pae group markedly increased the average daily gain (ADG) and zonula occludens-1 (ZO-1) mRNA expression (P < 0.05). In the 0.2% and 0.4% Pae groups, the feed-to-gain ratio (F/G) was significantly reduced and the mRNA expression levels of Caspase-8, respectively, markedly enhanced the mRNA expression levels of transforming growth factor-β (TGF-β) and interleukins-4 (IL-4) (P < 0.05). In the 0.8% Pae group, the relative abundance of Campilobacterota was significantly reduced (P < 0.05). In the 0.4% Pae group, the relative abundance of Firmicutes was notably increased (P < 0.05). In the 0.2 and 0.8% Pae groups, the relative abundance of Prevotella was markedly increased (P < 0.05). In the 0.2% Pae group, the contents of propionic acid, butyric acid, and valerate acid were markedly higher (P < 0.05). Thus, it is speculated that Pae may regulate the balance of anti-inflammatory/pro-inflammatory factors, improve intestinal tight junction expression, reduce apoptosis, and improve intestinal microflora structure and growth performance of piglets, thereby restoring intestinal barrier function and alleviating DSS-induced UC in piglets.
Assessment of Sustainable Elimination Criteria for Iodine Deficiency Disorders Recommended by International Organizations
Authors: Fan Lijun , Meng Fangang , Sun Qihao , Zhai Yuqian , Liu Peng
Published: April 2022

Enormous efforts have been made to evaluate the worldwide prevention and control of iodine deficiency disorders (IDDs). This study evaluated China's achievements in IDD prevention and control against WHO criteria for sustainable elimination of IDD. The study sample consisted of 556,390 school-aged children and 271,935 pregnant women enrolled in the 2018 China National IDD Surveillance. As a result, at the national level, median urine iodine concentration (MUIC) was 206.1 and 163.5 μg/l in children and in pregnant women, respectively. The proportion of households consuming adequate iodized salt (PHCAIS) was 90.2%. The prevalence rates of goiter in children and thyroid disease in pregnant women were 2.0 and 0.8%, respectively. MUIC showed significant non-linear increasing trends with increasing PHCAIS in both children and pregnant women. The prevalence of thyroid disease in pregnant women had a sharp decreasing trend with increasing PHCAIS. Of note, the prevalence of goiter in children and thyroid disease in pregnant women against MUIC both presented as significant U-shaped curves, with the lowest prevalence at 100–300 μg/l of MUIC in children and 150–250 μg/l in pregnant women. PHCAIS, MUIC, and the programmatic indicators at the national level were all above their cut-offs proposed in the 2007 Criteria. Evaluation by adding the prevalence of goiter (<5%) yielded the different results at the county level. Sustainable elimination of IDD has been achieved nationally. 2018 Chinese surveillance data support the expansion of global cut-offs for optimal iodine status in school-age children from 100–199 to 100–299 μg/l as recommended by others and the lower limit of MUIC (150 μg/l) in pregnant women also seems justified. Inclusion of goiter prevalence <5% in our analysis reduced the number of municipalities and counties which had achieved sustainable elimination of IDD.
Glioblastoma Following Treated Medulloblastoma After 29 Years in the Posterior Fossa: Case Report and Review of Literature
Authors: Mesbahi Tarek , Zaine Hind , Mahazou Abdou Ismaël , Chekrine Tarik , Sahraoui Souha , Karkouri Mehdi , Lakhdar Abdelhakim
Published: April 2022

Glioblastoma multiforme (GBM) is a high-grade glioma that may be a rare complication of radiotherapy. We report a case of a patient who was treated for medulloblastoma (MB) of the posterior fossa at the age of 27 years. Twenty-nine years later, at the age of 56 years, he presented with a double-location tumor: supratentorial and in the posterior fossa. Imaging features of the supratentorial location were very suggestive of a meningioma. We operated on the posterior fossa location, which revealed a glioblastoma. Histologically, the tumor cells exhibited characteristics of both GBM and rhabdoid tumor cells. Literature reports of cases of GBM following MB at the same place are very rare, and presenting rhabdoid characteristics is even rarer. This is the first case of MB and GBM at ages 27 and 56 years, respectively. The double-location supratentorial probable meningioma and GBM of the posterior fossa 32 years after MB is the only case reported in the literature. What to do in this case remains a topic of debate, and there are no clear recommendations in the literature.
P4HA1 Regulates CD31 via COL6A1 in the Transition of Glioblastoma Stem-Like Cells to Tumor Endothelioid Cells
Authors: Han Xiangming , Wang Qiyan , Fang Sheng , Wang Jialin , Liu Fusheng , Zhang Junwen , Jin Guishan
Published: April 2022

Glioblastoma multiforme (GBM) is a common intracranial malignancy characterized by abundant and aberrant vasculature. The efficiency of existing antivascular treatments remains unsatisfactory. The transition of glioblastoma stem-like cells (GSCs) into tumor endothelioid cells (ECs) has been thought to cause glioma neovascularization and anti-angiogenesis tolerance, but the mechanisms regulating glioma transdifferentiation remains unclear. Our previous study found that P4HA1 regulates GSCs vascular mimicry in a hypoxic microenvironment, but the detailed molecular mechanism has not been determined. In this study, candidate protein COL6A1 was screened by mass spectrometry. In vitro experiments show that P4HA1 regulates the expression of CD31 via COL6A1, with the levels of expression of P4HA1, COL6A1 and the vascular endothelial molecular markers CD31 showing positive correlations in vivo assay. Altering the expression of P4HA1 in GSCs altered the expression of COL6A1 and CD31, thereby inducing glioma angiogenesis. In conclusion, this study revealed that the P4HA1/COL6A1 axis modulates the transdifferentiation process of GSCs into ECs. Interrupting this signaling axis can inhibit glioma angiogenesis, suggesting that this axis may be a novel target for antivascular therapy in patients with glioma.
Pheochromocytoma Mimicking Acute Coronary Syndrome: A Case Report
Authors: Cheng Yanwei , Qin Lijie , Chen Long
Published: April 2022

Pheochromocytoma is a rare catecholamine-secreting tumor with highly variable clinical presentations. We herein report a patient who presented to the emergency department with precordia pain, elevated myocardial enzymes, T-wave inversions on electrocardiogram and segmental ventricular wall motion abnormalities on echocardiography, which is normally managed as suspected acute coronary syndrome (ACS). However, the urgent coronary angiography showed normal coronary arteries. During his hospital stay, a sudden increase in blood pressure allowed us to suspect a pheochromocytoma, which was confirmed by elevated levels of catecholamines and by the finding of a right adrenal mass on magnetic resonance imaging. The tumor was successfully excised and the patient is now asymptomatic. This case illustrates that pheochromocytoma can present as a mimic of ACS but this is often difficult to diagnose at first glance and often misleads clinicians into making an incorrect diagnosis. In addition, clinicians should be familiar with clinical manifestations of pheochromocytoma, which can help raise clinical suspicion and facilitate the early diagnosis and treatment of pheochromocytoma.
GPX4 Plays a Crucial Role in Fuzheng Kang’ai Decoction-Induced Non-Small Cell Lung Cancer Cell Ferroptosis
Authors: Zhao Yue-Yang , Yang Yu-Qi , Sheng Hong-Hao , Tang Qing , Han Ling , Wang Su-Mei , Wu Wan-Yin
Published: April 2022

Background: Fuzheng Kang’ai decoction (FZKA) has been widely used to treat Non-Small Cell Lung Cancer (NSCLC) patients in China for decades, showing definitively curative effects in clinic. Recently, we found that FZKA could induce NSCLC cell ferroptosis, another type of programmed cell death (PCD), which is totally different from cell apoptosis. Therefore, in the present study, we aim to discover the exact mechanism by which FZKA induces NSCLC cell ferroptosis, which is rarely studied in Traditional Chinese Medicine (TCM).

Methods: Cell proliferation assay were performed to detect the cell viability. Cell ferroptosis triggered by FZKA was observed by performing lipid peroxidation assay, Fe2+ Ions assay, and mitochondrial ultrastructure by transmission electron microscopy. Ferroptosis inhibitors including liproxstatin-1 and UAMC 3203 were used to block ferroptosis. The ratio of GSH/GSSG was done to measure the alteration of oxidative stress. Western blot and qRT-PCR were carried out to detect the expression of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2) and glutathione peroxidase 4 (GPX4) at protein and mRNA levels, respectively. Lentivirus transfection was performed to overexpress GPX4 stably. Animal model was done to verify the effect of FZKA-induced ferroptosis in NSCLC in vivo and immunohistochemistry was done to detect the expression of SLC7A11, SLC3A2 and GPX4 at protein level.

Results: First of all, in vitro experiments confirmed the inhibition effect of FZKA on NSCLC cell growth. We then, for the first time, found that FZKA induced NSCLC cell ferroptosis by increasing lipid peroxidation and cellular Fe2+ Ions. Moreover, characteristic morphological changes of NSCLC cell ferroptosis was observed under transmission electron microscopy. Mechanistically, GPX4, as a key inhibitor of lipid peroxidation, was greatly suppressed by FZKA treatment both at protein and mRNA levels. Furthermore, system xc− (SLC7A11 and SLC3A2) were found to be suppressed and a decreased GSH/GSSG ratio was observed at the same time when treated with FZKA. Notably, overexpressing GPX4 reversed the effect of FZKA-induced NSCLC cell ferroptosis significantly. Finally, the above effect was validated using animal model in vivo.

Conclusion: Our findings conclude that GPX4 plays a crucial role in FZKA-induced NSCLC cell ferroptosis, providing a novel molecular mechanism by which FZKA treats NSCLC.
Image Analysis of the Mitochondrial Network Morphology With Applications in Cancer Research
Authors: Chu Ching-Hsiang , Tseng Wen-Wei , Hsu Chan-Min , Wei An-Chi
Published: April 2022

Mitochondria are dynamic organelles that integrate bioenergetics, biosynthesis, and signaling in cells and regulate redox homeostasis, apoptotic pathways, and cell proliferation and differentiation. Depending on the environmental conditions, the mitochondrial morphology dynamically changes to match the energy demands. The mitochondrial dynamics is related to the initiation, migration, and invasion of diverse human cancers and thus affects cancer metastasis, metabolism, drug resistance, and cancer stem cell survival. We reviewed the current image-based analytical tools and machine-learning techniques for phenotyping mitochondrial morphology in different cancer cell lines from confocal microscopy images. We listed and applied pipelines and packages available in ImageJ/Fiji, CellProfiler, MATLAB, Java, and Python for the analysis of fluorescently labeled mitochondria in microscopy images and compared their performance, usability and applications. Furthermore, we discussed the potential of automatic mitochondrial segmentation, classification and prediction of mitochondrial abnormalities using machine learning techniques. Quantification of the mitochondrial morphology provides potential indicators for identifying metabolic changes and drug responses in cancer cells.
Acute Oxygen-Sensing via Mitochondria-Generated Temperature Transients in Rat Carotid Body Type I Cells
Authors: Rakoczy Ryan J. , Schiebrel Clay M. , Wyatt Christopher N.
Published: April 2022

The Carotid Bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Herein, preliminary evidence is presented supporting a novel oxygen-sensing hypothesis which suggests CB Type I cell “hypoxic signaling” may in part be mediated by mitochondria-generated thermal transients in TASK-channel-containing microdomains. Distances were measured between antibody-labeled mitochondria and TASK-potassium channels in primary rat CB Type I cells. Sub-micron distance measurements (TASK-1: 0.33 ± 0.04 µm, n = 47 vs TASK-3: 0.32 ± 0.03 µm, n = 54) provided evidence for CB Type I cell oxygen-sensing microdomains. A temperature-sensitive dye (ERthermAC) indicated that inhibition of mitochondrial activity in isolated cells caused a rapid and reversible inhibition of mitochondrial thermogenesis and thus temperature in these microdomains. Whole-cell perforated-patch current-clamp electrophysiological recordings demonstrated sensitivity of resting membrane potential (Vm) to temperature: lowering bath temperature from 37°C to 24°C induced consistent and reversible depolarizations (Vm at 37°C: -48.4 ± 4.11 mV vs 24°C: -31.0 ± 5.69 mV; n = 5; p < 0.01). These data suggest that hypoxic inhibition of mitochondrial thermogenesis may play an important role in oxygen chemotransduction in the CB. A reduction in temperature within cellular microdomains will inhibit plasma membrane ion channels, influence the balance of cellular phosphorylation–dephosphorylation, and may extend the half-life of reactive oxygen species. The characterization of a thermosensory chemotransduction mechanism, that may also be used by other oxygen-sensitive cell types and may impact multiple other chemotransduction mechanisms is critical if we are to fully understand how the CBs, and potentially other oxygen-sensitive cells, respond to hypoxia.