Research Progress of Eye Movement Analyses and its Detection Algorithms in Alzheimer's Disease.

Alzheimer's disease (AD) has been considered one of the most challenging forms of dementia. The earlier the people are diagnosed with AD, the easier it is for doctors to find a treatment. Based on the previous literature summarizing the research results on the relationship between eye movement and AD before 2013, this paper reviewed 34 original eye movements research papers only closely related to AD published in the past ten years and pointed out that the prosaccade (4 papers) and antisaccade (5 papers) tasks, reading tasks (3 papers), visual search tasks (3 papers) are still the research objects of many researchers, Some researchers have looked at King-Devick tasks (2 papers), reading tasks (3 papers) and special tasks (8 papers), and began to use combinations of different saccade tasks to detect the relationship between eye movement and AD, which had not been done before. These reflect the diversity of eye movement tasks and the complexity and difficulty of the relationship between eye movement and AD. On this basis, the current processing and analysis methods of eye movement datasets are analyzed and discussed in detail, and we note that certain key data that may be especially important for the early diagnosis of AD by using eye movement studies cannot be miss-classified as noise and removed. Finally, we note that the development of methods that can accurately denoise and classify and quickly process massive eye movement data is quite significant for detecting eye movements in early diagnosis of AD.

Hydrogen Sulfide Alleviates Oxidative Damage under Chilling Stress through Mitogen-Activated Protein Kinase in Tomato.

Tomato is the vegetable with the largest greenhouse area in China, and low temperature is one of the main factors affecting tomato growth, yield, and quality. Hydrogen sulfide (H2S) plays an important role in regulating plant chilling tolerance, but its downstream cascade reaction and mechanism remain unclear. Mitogen-activated protein kinases (MAPK/MPKs) are closely related to a variety of signaling substances in stress signal transmission. However, whether H2S is related to the MPK cascade pathway in response to low-temperature stress is rarely reported. In this study, NaHS treatment significantly decreased the electrolyte leakage (EL), superoxide anion (O2-) production rate, and hydrogen peroxide (H2O2) content of seedlings at low temperatures. In addition, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were obviously increased; and the photochemical efficiency of PSII (Fv/Fm) was enhanced with treatment with NaHS, indicating that NaHS improved the seedlings' cold tolerance by alleviating the degree of membrane lipid peroxidation and oxidative damage. However, H2S scavenger hypotaurine (HT) treatment showed the opposite effect. We found that H2S content, L-cysteine desulfhydrase (LCD) activity, and mRNA expression were increased by chilling stress but reduced by MPK inhibitor PD98059; PD98059 reversed the alleviating effect of H2S via increasing the EL and H2O2 contents. The expression levels of MPK1-MPK7 at low temperatures showed that SlMPK4 was significantly induced by exogenous NaHS and showed a trend of first increasing and then decreasing, while the expression level of SlMPK4 in HT-treated seedlings was lower than that of the control. After SlMPK4 was silenced by virus-induced gene silencing, the H2S-induced upregulation of C-repeat-Binding Factor (CBF1), inducer of CBF expression 1 (ICE1), respiratory burst oxidase homologs (RBOH1, RBOH2) at low temperatures disappeared, and tomato cold tolerance decreased. In conclusion, H2S improves the cold tolerance of tomato plants by increasing the activity of antioxidant enzymes and reducing reactive oxygen species (ROS) accumulation and membrane lipid peroxidation. MPK4 may act as a downstream signaling molecule in this process.

Involvement of Type 10 17ß-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer's Disease.

Type 10 17ß-hydroxysteroid dehydrogenase (17ß-HSD10) is the HSD17B10 gene product playing an appreciable role in cognitive functions. It is the main hub of exercise-upregulated mitochondrial proteins and is involved in a variety of metabolic pathways including neurosteroid metabolism to regulate allopregnanolone homeostasis. Deacetylation of 17ß-HSD10 by sirtuins helps regulate its catalytic activities. 17ß-HSD10 may also play a critical role in the control of mitochondrial structure, morphology and dynamics by acting as a member of the Parkin/PINK1 pathway, and by binding to cyclophilin D to open mitochondrial permeability pore. 17ß-HSD10 also serves as a component of RNase P necessary for mitochondrial tRNA maturation. This dehydrogenase can bind with the Aß peptide thereby enhancing neurotoxicity to brain cells. Even in the absence of Aß, its quantitative and qualitative variations can result in neurodegeneration. Since elevated levels of 17ß-HSD10 were found in brain cells of Alzheimer's disease (AD) patients and mouse AD models, it is considered to be a key factor in AD pathogenesis. Since data underlying Aß-binding-alcohol dehydrogenase (ABAD) were not secured from reported experiments, ABAD appears to be a fabricated alternative term for the HSD17B10 gene product. Results of this study would encourage researchers to solve the question why elevated levels of 17ß-HSD10 are present in brains of AD patients and mouse AD models. Searching specific inhibitors of 17ß-HSD10 may find candidates to reduce senile neurodegeneration and open new approaches for the treatment of AD.

The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity.

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with ß-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.

Biological Characteristics and Functional Analysis of the Linoleic Acid Synthase Gene ZjFAD2 in Jujube.

Jujube fruit is rich in linoleic acid and other bioactive components and has great potential to be used for the development of functional foods. However, the roles of FAD2 genes in linoleic acid biosynthesis in jujube fruit remain unclear. Here, we identified 15 major components in jujube and found that linoleic acid was the main unsaturated fatty acid; major differences in the content and distribution of linoleic acid in the pulp and seeds were observed, and levels of linoleic acid decreased during fruit maturation. Analysis of the fatty acid metabolome, genome, and gene expression patterns of cultivated and wild-type jujube revealed five ZjFAD2 family members highly related to linoleic acid biosynthesis. The heterologous expression of these five ZjFAD2 family members in tobacco revealed that all five of these genes increased the content of linoleic acid. Additionally, transient expression of these genes in jujube fruit and the virus-induced gene silencing (VIGS) test further confirmed the key roles of ZjFAD2-11 and ZjFAD2-1 in the biosynthesis of linoleic acid. The results of this research provide valuable insights into the molecular mechanism underlying linoleic acid synthesis in jujube and will aid the development of quality-oriented breeding strategies.

Nickel Nanoparticles Induced Hepatotoxicity in Mice via Lipid-Metabolism-Dysfunction-Regulated Inflammatory Injury.

Nickel nanoparticles (NiNPs) have wide applications in industry and biomedicine due to their unique characteristics. The liver is the major organ responsible for nutrient metabolism, exogenous substance detoxification and biotransformation of medicines containing nanoparticles. Hence, it is urgent to further understand the principles and potential mechanisms of hepatic effects on NiNPs administration. In this study, we explored the liver impacts in male C57/BL6 mice through intraperitoneal injection with NiNPs at doses of 10, 20 and 40 mg/kg/day for 7 and 28 days. The results showed that NiNPs treatment increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and induced pathological changes in liver tissues. Moreover, hepatic triglyceride (TG) content and lipid droplet deposition identified via de novo lipogenesis (DNL) progression were enhanced after NiNPs injection. Additionally, sustained NiNPs exposure induced a remarkable hepatic inflammatory response, significantly promoted endoplasmic reticulum stress (ER stress) sensors Ire1α, Perk and Atf6, and activated the occurrence of liver cell apoptosis. Overall, the research indicated that NiNPs exposure induced liver injury and disturbance of lipid metabolism. These findings revealed the public hazard from extreme exposure to NiNPs and provided new information on biological toxicity and biosafety evaluation.

Infantile Neurodegeneration Results from Mutants of 17ß-Hydroxysteroid Dehydrogenase Type 10 Rather Than Aß-Binding Alcohol Dehydrogenase.

Type 10 17ß-hydroxysteroid dehydrogenase (17ß-HSD10), a homo-tetrameric multifunctional protein with 1044 residues encoded by the HSD17B10 gene, is necessary for brain cognitive function. Missense mutations result in infantile neurodegeneration, an inborn error in isoleucine metabolism. A 5-methylcytosine hotspot underlying a 388-T transition leads to the HSD10 (p.R130C) mutant to be responsible for approximately half of all cases suffering with this mitochondrial disease. Fewer females suffer with this disease due to X-inactivation. The binding capability of this dehydrogenase to Aß-peptide may play a role in Alzheimer's disease, but it appears unrelated to infantile neurodegeneration. Research on this enzyme was complicated by reports of a purported Aß-peptide-binding alcohol dehydrogenase (ABAD), formerly referred to as endoplasmic-reticulum-associated Aß-binding protein (ERAB). Reports concerning both ABAD and ERAB in the literature reflect features inconsistent with the known functions of 17ß-HSD10. It is clarified here that ERAB is reportedly a longer subunit of 17ß-HSD10 (262 residues). 17ß-HSD10 exhibits L-3-hydroxyacyl-CoA dehydrogenase activity and is thus also referred to in the literature as short-chain 3-hydorxyacyl-CoA dehydrogenase or type II 3-hydorxyacyl-CoA dehydrogenase. However, 17ß-HSD10 is not involved in ketone body metabolism, as reported in the literature for ABAD. Reports in the literature referring to ABAD (i.e., 17ß-HSD10) as a generalized alcohol dehydrogenase, relying on data underlying ABAD's activities, were found to be unreproducible. Furthermore, the rediscovery of ABAD/ERAB's mitochondrial localization did not cite any published research on 17ß-HSD10. Clarification of the purported ABAD/ERAB function derived from these reports on ABAD/ERAB may invigorate this research field and encourage new approaches to the understanding and treatment of HSD17B10-gene-related disorders. We establish here that infantile neurodegeneration is caused by mutants of 17ß-HSD10 but not ABAD, and so we conclude that ABAD represents a misnomer employed in high-impact journals.

Identification of GnRH-like peptide and its potential signaling pathway involved in the oocyte meiotic maturation in the Chinese mitten crab, Eriocheir sinensis.

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in reproductive regulation in vertebrates. However, GnRH was rarely isolated and its function remains poorly characterized in invertebrates. The existence of GnRH in ecdysozoa has been controversial for a long. Here, we isolated and identified two GnRH-like peptides from brain tissues in Eriocheir sinensis. Immunolocalization showed that the presence of EsGnRH-like peptide in brain, ovary and hepatopancreas. Synthetic EsGnRH-like peptides can induce germinal vesicle breakdown (GVBD) of oocyte. Similar to vertebrates, ovarian transcriptomic analysis revealed a GnRH signaling pathway in the crab, in which most genes exhibited dramatically high expression at GVBD. RNAi knockdown of EsGnRHR suppressed the expression of most genes in the pathway. Co-transfection of the expression plasmid for EsGnRHR with reporter plasmid bearing CRE-luc or SRE-luc response element into 293T cells showed that EsGnRHR transduces its signal via cAMP and Ca2+ signaling transduction pathways. In vitro incubation of the crab oocyte with EsGnRH-like peptide confirmed the cAMP-PKA cascade and Ca2+ mobilization signaling cascade but lack of a PKC cascade. Our data present the first direct evidence of the existence of GnRH-like peptides in the crab and demonstrated its conserved role in the oocyte meiotic maturation as a primitive neurohormone.

The correlation of the neutrophil-lymphocyte ratio to clinical and imaging parameters in patients with thyroid eye disease.

Thyroid eye disease (TED) is the major extrathyroidal manifestation of Graves' disease (GD). Treatment choice is based on clinical activity and severity of TED, as evaluated with clinical activity score (CAS) and magnetic resonance (MR) imaging. We aimed to determine the relationship between neutrophil-to-lymphocyte ratio (NLR), a readily available indicator of systemic inflammation, and clinical and MR imaging parameters in TED patients. Eighty-seven consecutive TED patients were included. The average signal intensity ratio (SIR), average extraocular muscle (EOM) diameter, and proptosis of the study eye were extracted from MR images. A baseline NLR ≥ 2.0 was recorded in 37 (42.5%) patients and NLR < 2.0 in 50 (57.5%) patients. TED patients with NLR ≥ 2.0 were older, had a higher CAS, average SIR, average EOM diameter and proptosis, and a lower serum thyrotrophin receptor antibody level than patients with NLR < 2.0 (all P < 0.05). All MR parameters showed significant correlation with CAS (P < 0.05). NLR correlated significantly with CAS (P = 0.001), average SIR (P = 0.004), average EOM diameter (P = 0.007), and proptosis (P = 0.007). Multiple regression revealed a significant correlation between NLR and CAS (P = 0.001), average SIR (P = 0.029), and proptosis (P = 0.037). Cox regression analysis showed that a high NLR at baseline was associated with a worse clinical outcome of TED (hazard ratio 3.7, 95% CI 1.22-11.2, P = 0.02), at a median follow-up of 25 months. In conclusion, NLR was correlated with CAS and MR imaging parameters and was associated with a worse clinical outcome of TED at follow-up in patients with TED. Additional prospective studies are needed to validate our findings.

Intrinsic Network Changes in Bilateral Tinnitus Patients with Cognitive Impairment: A Resting-State Functional MRI Study.

Previous studies have found a link between tinnitus and cognitive impairment, even leading to dementia. However, the mechanisms underlying this association are not clear. The purpose of this study was to explore intrinsic network changes in tinnitus and hearing loss patients with cognitive disorders. We included 17 individuals with bilateral idiopathic tinnitus, hearing loss, and cognitive impairment (PA) and 21 healthy controls. We identified resting-state networks (RSNs) and measured intra-network functional connectivity (FC) values via independent component analysis (ICA). We also evaluated correlations between RSNs and clinical characteristics. Compared with the healthy controls, the PA group showed decreased connectivity within the ventral attention network, dorsal attention network (DAN), visual network, left frontoparietal network, right frontoparietal network, sensorimotor network, and increased connectivity within the executive control network. MoCA (Montreal Cognitive Assessment) scores were negatively correlated with the FC values for left calcarine within the DAN. We identified abnormal intrinsic connectivity in several brain networks, mainly involving cognitive control, vision, sensorimotor function, and the cerebellum, in tinnitus patients with cognitive impairment. It may be possible to use the FC strength of the left calcarine within the DAN as an imaging marker to predict cognitive impairment in tinnitus patients.

Automated Screening of COVID-19-Based Tongue Image on Chinese Medicine.

Objective: Artificial intelligence-powered screening systems of coronavirus disease 2019 (COVID-19) are urgently demanding since the ongoing outbreak of SARS-CoV-2 worldwide. Chest CT or X-ray is not sufficient to support the large-scale screening of COVID-19 because mildly-infected patients do not have imaging features on these images. Therefore, it is imperative to exploit supplementary medical imaging strategies. Traditional Chinese medicine has played an essential role in the fight against COVID-19. Methods: In this paper, we conduct two kinds of verification experiments based on a newly-collected multi-modality dataset, which consists of three types of modalities: tongue images, chest CT scans, and X-ray images. First, we study a binary classification experiment on tongue images to verify the discriminative ability between COVID-19 and non-COVID-19. Second, we design extensive multimodality experiments to validate whether introducing tongue image can improve the screening accuracy of COVID-19 based on chest CT or X-ray images. Results: Tongue image screening of COVID-19 showed that the accuracy (ACC), sensitivity (SEN), specificity (SPEC), and Matthew correlation coefficient (MCC) of the improved AlexNet and Googlenet both reached 98.39%, 98.97%, 96.67%, and 99.11%. The fusion of chest CT and tongue images used a tandem multimodal classifier fusion strategy to achieve optimal classification, and the results and screening accuracy of COVID-19 reached 98.98%, resulting in a significant improvement of 4.75% the highest accuracy in 375 years compared with the single-modality model. The fusion of chest x-rays and tongue images also had good classification accuracy. Conclusions: Both experimental results demonstrate that tongue image not only has an excellent discriminative ability for screening COVID-19 but also can improve the screening accuracy based on chest CT or X-rays. To the best of our knowledge, it is the first work that verifies the effectiveness of tongue image on screening COVID-19. This paper provides a new perspective and a novel solution that contributes to large-scale screening toward fast stopping the pandemic of COVID-19.

3-Hydroxyacyl-CoA and Alcohol Dehydrogenase Activities of Mitochondrial Type 10 17ß-Hydroxysteroid Dehydrogenase in Neurodegeneration Study.

BACKGROUND: Mitochondrial 17ß-hydroxysteroid dehydrogenase type 10 (17ß-HSD10) is necessary for brain cognitive function, but its studies were confounded by reports of Aß-peptide binding alcohol dehydrogenase (ABAD), formerly endoplasmic reticulum-associated Aß-peptide binding protein (ERAB), for two decades so long as ABAD serves as the alternative term of 17ß-HSD10. OBJECTIVE: To determine whether those ABAD reports are true or false, even if they were published in prestigious journals. METHODS: 6xHis-tagged 17ß-HSD10 was prepared and characterized by well-established experimental procedures. RESULTS: The N-terminal 6xHis tag did not significantly interfere with the dehydrogenase activities of 17ß-HSD10, but the kinetic constants of its 3-hydroxyacyl-CoA dehydrogenase activity are drastically distinct from those of ABAD, and it was not involved in ketone body metabolism as previously reported for ABAD. Furthermore, it was impossible to measure its generalized alcohol dehydrogenase activities underlying the concept of ABAD because the experimental procedures described in ABAD reports violated basic chemical and/or biochemical principles. More incredibly, both authors and journals had not yet agreed to make any corrigenda of ABAD reports. CONCLUSION: Brain 17ß-HSD10 plays a key role in neurosteroid metabolism and further studies in this area may lead to potential treatments of neurodegeneration including AD.

Intrinsic network changes associated with cognitive impairment in patients with hearing loss and tinnitus: a resting-state functional magnetic resonance imaging study.

Background: Hearing loss and tinnitus often occur concurrently and play a vital role in the development and progression of cognitive impairment (CI). However, the exact mechanism remains unclear. This study aimed to investigate the changes in intrinsic brain connectivity in patients with hearing loss and tinnitus accompanied by CI. Methods: A total of 24 hearing loss and tinnitus patients with CI, 23 hearing loss and tinnitus patients with cognitive normality (CN), and 20 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Resting-state networks (RSNs) were identified and intrinsic functional connectivity (FC) values were measured using independent component analysis (ICA). FC values within the RSNs were measured and correlations between altered RSNs and clinical characteristics were evaluated using Pearson correlation analysis. Results: No significant difference was found in the disease duration or Tinnitus Handicap Inventory (THI) scores between the CI and CN groups. Eleven RSNs differed significantly among the 3 groups. Compared with the CN group, the CI group exhibited higher FC in the right supramarginal and left middle temporal gyri within the auditory network (AN), the left inferior parietal, but supramarginal and angular gyrus (IPL) gyrus within the right frontoparietal network (RFPN), the right middle occipital gyrus (R_MOG) and left superior frontal gyrus (L_SFG) within the dorsal attention network (DAN), the right middle frontal gyrus (R_MFG) within the executive control network (ECN), the right cuneus (R_cuneus) within the visual network (VN), and the left inferior frontal gyrus within the salience network (SAN), as well as lower FC in the right superior temporal gyrus (R_STG) within the AN and the left FPN (LFPN) and the right superior frontal gyrus (R_SFG) within the LFPN. Montreal Cognitive Assessment (MoCA) scores were negatively correlated with the FC values of the R_MFG and positively correlated with the FC values of the R_STG and R_SFG. Conclusions: Aberrant intrinsic FC was observed in the R_MFG within the ECN, the R_STG within the AN, and the R_SFG within the LFPN in hearing loss and tinnitus patients, which may be a biomarker for the severity of CI in hearing loss and tinnitus patients.

Mitolysosome exocytosis, a mitophagy-independent mitochondrial quality control in flunarizine-induced parkinsonism-like symptoms.

Mitochondrial quality control plays an important role in maintaining mitochondrial homeostasis and function. Disruption of mitochondrial quality control degrades brain function. We found that flunarizine (FNZ), a drug whose chronic use causes parkinsonism, led to a parkinsonism-like motor dysfunction in mice. FNZ induced mitochondrial dysfunction and decreased mitochondrial mass specifically in the brain. FNZ decreased mitochondrial content in both neurons and astrocytes, without affecting the number of nigral dopaminergic neurons. In human neural progenitor cells, FNZ also induced mitochondrial depletion. Mechanistically, independent of ATG5- or RAB9-mediated mitophagy, mitochondria were engulfed by lysosomes, followed by a vesicle-associated membrane protein 2- and syntaxin-4-dependent extracellular secretion. A genome-wide CRISPR knockout screen identified genes required for FNZ-induced mitochondrial elimination. These results reveal not only a previously unidentified lysosome-associated exocytosis process of mitochondrial quality control that may participate in the FNZ-induced parkinsonism but also a drug-based method for generating mitochondria-depleted mammal cells.

Functional changes in the visual cortex in preoperative and postoperative patients with intermittent exotropia: study protocol for a non-randomised case-control clinical trial.

INTRODUCTION: Intermittent exotropia (IXT) is the most common type of divergent squint. IXT is primarily a cortical neurologic dysfunction disorder, occurring as a result of the insufficient maintenance of sensory and motor fusion. Recent reports have demonstrated the relationship between IXT and visual cortical impairment. We planned to assess blood oxygen level-dependent (BOLD)-functional magnetic resonance imaging (fMRI) in patients with IXT during the preoperative and postoperative follow-ups to evaluate the functional changes in the visual cortex. METHODS AND ANALYSIS: A total of 90 Chinese subjects will be recruited, and their ages will be between 18 and 40 years old. The subjects will include the surgical treatment (ST) group (45 subjects with IXT who will undergo surgery) and the HC group (45 age-matched, sex-matched and education-matched healthy volunteers). The assessments will include the following aspects: fMRI and general ophthalmic examinations, optometry measurements and strabismus-related tests, such as the ocular deviation, binocular vision test and Newcastle Control Score (NCS). Each subject will complete the resting-state BOLD-fMRI, and the sequences will include echo planar imaging (EPI) pulse and 3-dimensional brain volume (3D-BRAVO) to acquire high-resolution images. The follow-up schedule will be 6 and 12 months after the surgery. The primary outcome will be determined by cortex changes in BOLD-fMRI in the ST group before and after surgery. We will also compare the HC group with the preoperative subjects in the ST group. The secondary outcomes will be changes in strabismus-related examinations, such as binocular visual function and NCS. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Ethics Committee of Beijing Tongren Hospital. We plan to publish the results of this study in a peer-reviewed journal article. TRIAL REGISTRATION NUMBER: ChiCTR2100048852.

Identification and characterization of a new germline-specific marker vasa gene and its promoter in the giant freshwater prawn Macrobrachium rosenbergii.

Vasa gene encodes a protein member of DEAD-box superfamily of ATP-dependent RNA helicases, which plays a key role in germline development in metazoans. In present study, we identified a new germline-specific marker Mrvasa in the prawn Macrobrachium rosenbergii, whose genomic DNA sequence consists of 14 exons and 13 introns. A 2516 bp of full-length Mrvasa cDNA encodes a protein of 603 amino acids. It contains nine conserved motifs, a zinc-finger motif, and RGG repeats. RT-PCR indicated that Mrvasa mRNA was specifically expressed in gonads. QPCR analysis further revealed that the expression of Mrvasa mRNA is much higher in testis than in ovary. In testis, the relative expression level of Mrvasa mRNA in late developing stage is significantly higher than that in early-middle developing stage. During ovarian development, no significant difference in expression was found. In situ hybridization demonstrated that Mrvasa mRNA was localized in germline cells including spermatogonia, spermatocytes, and spermatozoa in testes, and previtellogenic and vitellogenic oocytes in ovary. We then isolated the Mrvasa promoter and determined the transcription core region of this promoter. This is the first report on identification of vasa core promoter in crustaceans. Our results will provide a useful germline-specific marker Mrvasa for tracing germline cell formation and development in M. rosenbergii.

Evaluating automatic hand hygiene monitoring systems: A scoping review.

Objectives: To categorize the extant automatic hand hygiene monitoring systems (AHHMSs) and evaluate the capacity of each to provide information on compliance rates. Study design: Scoping review. Methods: Three international databases, PubMed, CINAHL, and EBSCO (between 1 January 2010 and 31 December 2020), were searched according to predetermined inclusion criteria for the scoping review. Two authors screened studies for eligibility independently. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Results: Twenty-seven studies were included. Three types of AHHMSs were identified: Type I provides information about the aggregate hand hygiene events (HHEs) only, while Type II adds aggregate hand hygiene opportunities (HHOs), and Type III presents both HHEs and HHOs for individuals. Results suggested that improving the accuracy of recording HHEs and/or HHOs was critical for improving the accuracy of the compliance, which could increase the acceptability of the monitoring system. In addition, the studies found that the implementation of AHHMSs, especially with prompt reminders or additional interventions, could improve the compliance significantly. Conclusions: The extant AHHMSs could be decomposed into components of 3Ps (product usage monitoring, position monitoring, and performance monitoring). By identifying devices and technology as well as the type of information provided for each component, our approach can aid healthcare facilities to choose a suitable AHHMS that meets their criteria.

Altered Spontaneous Brain Activity Patterns and Functional Connectivity in Adults With Intermittent Exotropia: A Resting-State fMRI Study.

The purpose of this study is to investigate brain functional changes in patients with intermittent exotropia (IXT) by analyzing the amplitude of low-frequency fluctuation (ALFF) of brain activity and functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI). There were 26 IXT patients and 22 age-, sex-, education-, and handedness-matched healthy controls (HCs) enrolled who underwent rs-fMRI. The ALFF, fractional ALFF (fALFF) values in the slow 4 and slow 5 bands, and FC values were calculated and compared. The correlations between ALFF/fALFF values in discrepant brain regions and clinical features were evaluated. Compared with HCs, ALFF/fALFF values were significantly increased in the right angular gyrus (ANG), supramarginal gyrus (SMG), inferior parietal lobule (IPL), precentral gyrus (PreCG), and the bilateral inferior frontal gyri (IFG), and decreased in the right precuneus gyrus (PCUN), left middle occipital gyrus (MOG), and postcentral gyrus (PoCG) in IXT patients. The Newcastle Control Test score was negatively correlated with ALFF values in the right IFG (r = -0.738, p < 0.001). The duration of IXT was negatively correlated with ALFF values in the right ANG (r = -0.457, p = 0.049). Widespread increases in FC were observed between brain regions, mainly including the right cuneus (CUN), left superior parietal lobule (SPL), right rolandic operculum (ROL), left middle temporal gyrus (MTG), left IFG, left median cingulate gyrus (DCG), left PoCG, right PreCG, and left paracentral gyrus (PCL) in patients with IXT. No decreased FC was observed. Patients with IXT exhibited aberrant intrinsic brain activities and FC in vision- and eye movement-related brain regions, which extend current understanding of the neuropathological mechanisms underlying visual and oculomotor impairments in IXT patients.

The Effect of Degree of Temporal Bone Pneumatization on Sound Transmission of Pulsatile Tinnitus Induced by Sigmoid Sinus Diverticulum and/or Dehiscence: A Clinical and Experimental Study.

BACKGROUND: Although many studies have suggested that air cells may play an important role in sigmoid sinus diverticulum and/or dehiscence (SSDD)-induced pulsatile tinnitus (PT), the exact effects remain unclear. This study aims to quantitatively investigate the effect of different degrees of pneumatization of temporal bone on sound transmission from the sigmoid sinus to the tympanic cavity. METHODS: In the clinical study, 25 patients were enrolled to measure the sound intensity and frequency of SSDD-induced PT. In the experimental study, sound inputs at different frequencies at the dehiscent sigmoid plate were measured and compared among realistic object models of different degrees of pneumatization, when sound intensity in the tympanic cavity was fixed as the level of the PT sound intensity sensed by patients. RESULTS: The sound intensity sensed by PT patients was 34.0 ± 13.0 dB SPL, which represented the sound intensity in the tympanic cavity transmitted from the dehiscent sigmoid plate. In the experimental study, when sound received in the tympanic cavity was fixed at 34 dB SPL, the mean inputs of sound intensity at the dehiscent sigmoid plate were 46.9, 46.2, 45.2, 47.1, 57, 57.4, and 74.1 dB SPL in a hypo-pneumatized model; 42.6, 43, 41.5, 43.2, 47.3, 58.2, and 78.8 dB SPL in a moderately pneumatized model; 52.6, 52.8, 48.1, 61, 64.2, 82.4, and >87.3 dB SPL in a well-pneumatized model; and 47.2, 46.2, 45.4, 49.4, 54.9, 66.6, and 77.7 dB SPL in hyper-pneumatized model, with increased sound frequencies (125-8000 Hz). The mean sound transmission distances were 41.7 mm, 45.2 mm, 47.6 mm, and 48.4 mm in successively better pneumatized models. CONCLUSION: Sound reduces while passing through air cells and attenuation is lowest in the moderately pneumatized temporal bone, followed by the hypo- and hyper-pneumatized temporal bones, and the highest in the well-pneumatized temporal bone. Lower-frequency sound attenuation (≤1000 Hz) is less than that of higher-frequency sound (>1000 Hz).

A Combined Model of Human iPSC-Derived Liver Organoids and Hepatocytes Reveals Ferroptosis in DGUOK Mutant mtDNA Depletion Syndrome.

Mitochondrial DNA depletion syndrome (MDS) is a group of severe inherited disorders caused by mutations in genes, such as deoxyribonucleoside kinase (DGUOK). A great majority of DGUOK mutant MDS patients develop iron overload progressing to severe liver failure. However, the pathological mechanisms connecting iron overload and hepatic damage remains uncovered. Here, two patients' skin fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs) and then corrected by CRISPR/Cas9. Patient-specific iPSCs and corrected iPSCs-derived high purity hepatocyte organoids (iHep-Orgs) and hepatocyte-like cells (iHep) are generated as cellular models for studying hepatic pathology. DGUOK mutant iHep and iHep-Orgs, but not control and corrected one, are more sensitive to iron overload-induced ferroptosis, which can be rescued by N-Acetylcysteine (NAC). Mechanically, this ferroptosis is a process mediated by nuclear receptor co-activator 4 (NCOA4)-dependent degradation of ferritin in lysosome and cellular labile iron release. This study reveals the underlying pathological mechanisms and the viable therapeutic strategies of this syndrome, and is the first pure iHep-Orgs model in hereditary liver diseases.