Gut microbiome and metabolome to discover pathogenic bacteria and probiotics in ankylosing spondylitis.

Objective: Previous research has partially revealed distinct gut microbiota in ankylosing spondylitis (AS). In this study, we performed non-targeted fecal metabolomics in AS in order to discover the microbiome-metabolome interface in AS. Based on prospective cohort studies, we further explored the impact of the tumor necrosis factor inhibitor (TNFi) on the gut microbiota and metabolites in AS. Methods: To further understand the gut microbiota and metabolites in AS, along with the influence of TNFi, we initiated a prospective cohort study. Fecal samples were collected from 29 patients with AS before and after TNFi therapy and 31 healthy controls. Metagenomic and metabolomic experiments were performed on the fecal samples; moreover, validation experiments were conducted based on the association between the microbiota and metabolites. Results: A total of 7,703 species were annotated using the metagenomic sequencing system and by profiling the microbial community taxonomic composition, while 50,046 metabolites were identified using metabolite profiling. Differential microbials and metabolites were discovered between patients with AS and healthy controls. Moreover, TNFi was confirmed to partially restore the gut microbiota and the metabolites. Multi-omics analysis of the microbiota and metabolites was performed to determine the associations between the differential microbes and metabolites, identifying compounds such as oxypurinol and biotin, which were correlated with the inhibition of the pathogenic bacteria Ruminococcus gnavus and the promotion of the probiotic bacteria Bacteroides uniformis. Through experimental studies, the relationship between microbes and metabolites was further confirmed, and the impact of these two types of microbes on the enterocytes and the inflammatory cytokine interleukin-18 (IL-18) was explored. Conclusion: In summary, multi-omics exploration elucidated the impact of TNFi on the gut microbiota and metabolites and proposed a novel therapeutic perspective: supplementation of compounds to inhibit potential pathogenic bacteria and to promote potential probiotics, therefore controlling inflammation in AS.

The research advances in Kirsten rat sarcoma viral oncogene homolog (KRAS)-related cancer during 2013 to 2022: a scientometric analysis.

Introduction: Cancer represents a significant global public health concern. In recent years, the incidence of cancer has been on the rise worldwide due to various factors, including diet, environment, and an aging population. Simultaneously, advancements in tumor molecular biology and genomics have led to a shift from systemic chemotherapy focused on disease sites and morphopathology towards precise targeted therapy for driver gene mutations. Therefore, we propose a comprehensive review aimed at exploring the research hotspots and directions in the field of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant cancers over the past decade, providing valuable insights for cancer treatment strategies. Specifically, we aim to present an intellectual landscape using data obtained from the Web of Science (WoS) regarding KRAS mutation. Methods: Bibliometrix, VOSviewer, CiteSpace, and HistCite were employed to conduct scientometric analyses on national publications, influential authors, highly cited articles, frequent keywords, etc. Results: A total of 16,609 publications met the screening criteria and exhibited a consistent annual growth trend overall. Among 102 countries/regions, the United States occupied the vast majority share of the published volume. The journal Oncotarget had the highest circulation among all scientific publications. Moreover, the most seminal articles in this field primarily focus on biology and targeted therapies, with overcoming drug resistance being identified as a future research direction. Conclusion: The findings of the thematic analysis indicate that KRAS mutation in lung cancer, the prognosis following B-Raf proto-oncogene, serine/threonine kinase (BRAF) or rat sarcoma (RAS) mutations, and anti-epidermal growth factor receptor (EGFR)-related lung cancer are the significant hotspots in the given field. Considering the significant advancements made in direct targeting drugs like sotorasib, it is anticipated that interest in cancers associated with KRAS mutations will remain steadfast.

Stable Flexible Electronic Devices under Harsh Conditions Enabled by Double-Network Hydrogels Containing Binary Cations.

Hydrogels are increasingly used in flexible electronic devices, but the mechanical and electrochemical stabilities of hydrogel devices are often limited under specific harsh conditions. Herein, chemically/physically cross-linked double-network (DN) hydrogels containing binary cations Zn2+ and Li+ are constructed in order to address the above challenges. Double networks of chemically cross-linked polyacrylamide (PAM) and physically cross-linked κ-Carrageenan (κ-CG) are designed to account for the mechanical robustness while binary cations endow the hydrogels with excellent ionic conductivity and outstanding environmental adaptability. Excellent mechanical robustness and ionic conductivity (25 °C, 2.26 S·m-1; -25 °C, 1.54 S·m-1) have been achieved. Utilizing the DN hydrogels containing binary cations as signal-converting materials, we fabricated flexible mechanosensors. High gauge factors (resistive strain sensors, 2.4; capacitive pressure sensors, 0.82 kPa-1) and highly stable sensing ability have been achieved. Interestingly, zinc-ion hybrid supercapacitors containing the DN hydrogels containing binary cations as electrolytes have achieved an initial capacity of 52.5 mAh·g-1 at a current density of 3 A·g-1 and a capacity retention rate of 82.9% after 19,000 cycles. Proper working of the zinc-ion hybrid supercapacitors at subzero conditions and stable charge-discharge for more than 19,000 cycles at -25 °C have been demonstrated. Overall, DN hydrogels containing binary cations have provided promising materials for high-performance flexible electronic devices under harsh conditions.

Experimental study on the effect and mechanism of adipose stem cell-derived exosomes combined with botulinum toxin A on skin trauma in rats.

BACKGROUND: Adipose stem cell-derived exosomes (ADSC-EXO) and botulinum toxin type A (BTX-A) individually showed a therapeutic effect on skin wound repair. AIMS: This study investigated their synergistic effect on promoting skin wound healing in vitro and in vivo and the underlying molecular events. METHODS: ADSCs were isolated from Sprague-Dawley (SD) rats to obtain ADSC-EXO by ultrafiltration and ultracentrifugation and were confirmed using nanoparticle tracking analysis and transmission electron microscopy. Human skin fibroblasts (HSF) were cultured and treated with or without ADSC-EXO, BTX-A, or their combination. Changes in cell phenotypes and protein expression were analyzed using different in vitro assays, and a rat skin wound model was used to assess their in vivo effects. RESULTS: The isolated ADSC-EXO from primarily cultured ADSCs had a circular vesicle shape with a 30-180 nm diameter. Treatment of HSF with ADSC-EXO and/or BTX-A significantly accelerated HSF migration in vitro and skin wound healing in a rat model. Moreover, ADSC-EXO plus BTX-A treatment dramatically induced VEGFA expression but reduced COL III and COL I levels in vivo. ADSC-EXO and/or BTX-A treatment significantly upregulated TGF-ß3 expression on Day 16 after surgery but downregulated TGF-ß1 expression, suggesting that ADSC-EXO plus BTX-A promoted skin wound healing and reduced inflammatory cell infiltration. CONCLUSIONS: The ADSC-EXO plus BTX-A treatment demonstrated a synergistic effect on skin wound healing through upregulation of VEGF expression and the TGF-ß3/TGF-ß1 and COL III/COL I ratio.

Effects of Multiple High-Dose Methamphetamine Administration on Enteric Dopaminergic Neurons and Intestinal Motility in the Rat Model.

Several studies have identified the effects of methamphetamine (MA) on central dopaminergic neurons, but its effects on enteric dopaminergic neurons (EDNs) are unclear. The aim of this study was to investigate the effects of MA on EDNs and intestinal motility. Male Sprague-Dawley rats were randomly divided into MA group and saline group. The MA group received the multiple high-dose MA treatment paradigm, while the controls received the same saline treatment. After enteric motility was assessed, different intestinal segments (i.e., duodenum, jejunum, ileum, and colon) were taken for histopathological, molecular biological, and immunological analysis. The EDNs were assessed by measuring the expression of two dopaminergic neuronal markers, dopamine transporter (DAT) and tyrosine hydroxylase (TH), at the transcriptional and protein levels. We also used c-Fos protein, a marker of neural activity, to detect the activation of EDNs. MA resulted in a significant reduction in TH and DAT mRNA expression as well as in the number of EDNs in the duodenum and jejunum (p < 0.05). MA caused a dramatic increase in c-Fos expression of EDNs in the ileum (p < 0.001). The positional variability of MA effects on EDNs paralleled the positional variability of its effect on intestinal motility, as evidenced by the marked inhibitory effect of MA on small intestinal motility (p < 0.0001). This study found significant effects of MA on EDNs with locational variability, which might be relevant to locational variability in the potential effects of MA on intestinal functions, such as motility.

Therapeutic efficacy of sulforaphane in autism spectrum disorders and its association with gut microbiota: animal model and human longitudinal studies.

Introduction: Sulforaphane (SFN) has been found to alleviate complications linked with several diseases by regulating gut microbiota (GM), while the effect of GM on SFN for autism spectrum disorders (ASD) has not been studied. Therefore, this study aimed to investigate the relationship between the effects of SFN on childhood ASD and GM through animal model and human studies. Methods: We evaluated the therapeutic effects of SFN on maternal immune activation (MIA) induced ASD-like rat model and pediatric autism patients using three-chamber social test and OSU Autism Rating Scale-DSM-IV (OARS-4), respectively, with parallel GM analysis using 16SrRNA sequencing. Results: SFN significantly improved the sniffing times of ASD-like rats in the three-chamber test. For human participants, the average verbal or non-verbal communication (OSU-CO) scores of SFN group had changed significantly at the 12-wk endpoint. SFN was safe and no serious side effects after taking. GM changes were similar for both ASD-like rats and ASD patients, such as consistent changes in order Bacillales, family Staphylococcaceae and genus Staphylococcus. Although the gut microbiota composition was significantly altered in SFN-treated ASD-like rats, the alteration of GM was not evident in ASD patients after 12 weeks of SFN treatment. However, in the network analysis, we found 25 taxa correlated with rats' social behavior, 8 of which were associated with SFN treatment in ASD-like rats, For ASD patients, we found 35 GM abundance alterations correlated with improvements in ASD symptoms after SFN treatment. Moreover, family Pasteurellaceae and genus Haemophilus were found to be associated with SFN administration in the network analyses in both ASD-like rats and ASD patients. Discussion: These findings suggest that SFN could provide a novel avenue for preventing and treating ASD, and its therapeutic effects might be related to gut microbiota.

Gut brain interaction theory reveals gut microbiota mediated neurogenesis and traditional Chinese medicine research strategies.

Adult neurogenesis is the process of differentiation of neural stem cells (NSCs) into neurons and glial cells in certain areas of the adult brain. Defects in neurogenesis can lead to neurodegenerative diseases, mental disorders, and other maladies. This process is directionally regulated by transcription factors, the Wnt and Notch pathway, the extracellular matrix, and various growth factors. External factors like stress, physical exercise, diet, medications, etc., affect neurogenesis and the gut microbiota. The gut microbiota may affect NSCs through vagal, immune and chemical pathways, and other pathways. Traditional Chinese medicine (TCM) has been proven to affect NSCs proliferation and differentiation and can regulate the abundance and metabolites produced by intestinal microorganisms. However, the underlying mechanisms by which these factors regulate neurogenesis through the gut microbiota are not fully understood. In this review, we describe the recent evidence on the role of the gut microbiota in neurogenesis. Moreover, we hypothesize on the characteristics of the microbiota-gut-brain axis based on bacterial phyla, including microbiota's metabolites, and neuronal and immune pathways while providing an outlook on TCM's potential effects on adult neurogenesis by regulating gut microbiota.

Construction of Exosomes that Overexpress CD47 and Evaluation of Their Immune Escape.

Our general purpose was to provide a theoretical and practical foundation for the use of exosomes (EXOs) that have high levels of CD47 as stable and efficient drug carriers. Thus, we prepared EXOs from adipose tissue-derived mesenchymal stromal cells (ADMSCs) that had high levels of CD47 (EXOsCD47) and control EXOs (without CD47), and then compared their immune escape in vivo and their resistance to phagocytosis in vitro. Nanoflow cytometry was used to determine the CD47 level in these EXOs, and the amount of EXOsCD47 that remained in rat plasma at 3 h after intraperitoneal injection. Phagocytosis of the EXOs was also determined using in vitro rat macrophage bone marrow (RMA-BM) experiments. Our in vitro results showed that macrophages ingested significantly more control EXOs than EXOsCD47 (p < 0.01), with confirmation by ultra-high-definition laser confocal microscopy. Consistently, our in vivo results showed that rats had 1.377-fold better retention of EXOsCD47 than control EXOs (p < 0.01). These results confirmed that these engineered EXOsCD47 had improved immune escape. Our results therefore verified that EXOsCD47 had increased immune evasion relative to control EXOs, and have potential for use as drug carriers.

Highly efficient rDNA-mediated multicopy integration based on the dynamic balance of rDNA in Saccharomyces cerevisiae.

Engineered Saccharomyces cerevisiae strains are good cell factories, and developing additional genetic manipulation tools will accelerate construction of metabolically engineered strains. Highly repetitive rDNA sequence is one of two main sites typically used for multicopy integration of genes. Here, we developed a simple and high-efficiency strategy for rDNA-mediated multicopy gene integration based on the dynamic balance of rDNA in S. cerevisiae. rDNA copy number was decreased by pre-treatment with hydroxyurea (HU). Then, heterologous genes were integrated into the rDNA sequence. The copy number of the integrated heterologous genes increased along with restoration of the copy number of rDNA. Our results demonstrated that HU pre-treatment doubled the number of integrated gene copies; moreover, compared with removing HU stress during transformation, removing HU stress after selection of transformants had a higher probability of resulting in transformants with high-copy integrated genes. Finally, we integrated 18.0 copies of the xylose isomerase gene into the S. cerevisiae genome in a single step. This novel rDNA-mediated multicopy genome integration strategy provides a convenient and efficient tool for further metabolic engineering of S. cerevisiae.

Identification and Characterization of the Mitochondrial Replication Origin for Stable and Episomal Expression in Yarrowia lipolytica.

Episomal plasmids are crucial expression tools for recombinant protein production and genome editing. In Saccharomyces cerevisiae, 2-µm artificial plasmids with a high copy number have been developed and used in metabolic engineering and synthetic biology. However, in unconventional yeasts such as Yarrowia lipolytica, episomal expression relies on a chromosome replication system; this system has the disadvantages of genetic instability and low copy numbers. In this study, we identified and characterized replication origins from the mitochondrial DNA (mtDNA) of Y. lipolytica. A 516-bp mtDNA sequence, mtORI, was confirmed to mediate the autonomous replication of circular plasmids with high protein expression levels and hereditary stability. However, the nonhomologous end-joining pathway could interfere with mtORI plasmid replication and engender genetic heterogeneity. In the Po 1f ΔKu70 strain, the homogeneity of the mtORI plasmid was significantly improved, and the highest copy number reached 5.0 per cell. Overall, mitochondrial-origin sequences can be used to establish highly stable and autonomously replicating plasmids, which can be a powerful supplement to the current synthetic biology tool library and promote the development of Y. lipolytica as a microbial cell factory.

Longdan Xiegan Tang attenuates liver injury and hepatic insulin resistance by regulating the angiotensin-converting enzyme 2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The ancient Chinese herbal formula Longdan Xiegan Tang (LXT, also called Gentiana Longdancao Decoction to Drain the Liver) treats insulin resistance- and inflammation-associated liver injuries in clinical practice. AIM OF THE STUDY: To investigate the molecular mechanisms underlying LXT-elicited improvement of the liver injuries. MATERIALS AND METHODS: Male rats were co-treated with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) for eight weeks. Blood parameters were determined enzymatically or by ELISA. Gene/protein expression was analyzed by Real-Time PCR, Western blot and/or immunohistochemistry. RESULTS: LXT attenuated olanzapine-induced liver injury manifested by hyperactivities of plasma alanine aminotransferase and aspartate aminostransferase, hyperbilirubinemia and hypoalbuminemia. Furthermore, LXT improved hepatic insulin resistance that was indicated by hyperinsulinemia, the increased HOMA-IR index, and hepatic over-phosphorylation of Ser307 in insulin receptor substrate (IRS)1, Ser731 in IRS2, Tyr607 in phosphoinositide 3-kinase p85α and Ser473 in AKT at baseline. Mechanistically, LXT inhibited olanzapine-triggered hepatic over-phosphorylation of both IκB kinase (IKK)α/ß and nuclear factor (NF)κB p65 proteins, and mRNA overexpression of tumor necrosis factor α, interleukin 6, interleukin 1ß and CD68. More importantly, LXT restored the decreases in angiotensin-converting enzyme 2 (ACE2) protein level, and its downstream targets Ang (1-7) content and Mas receptor expression. CONCLUSIONS: The present results demonstrate that LXT attenuates liver injury and hepatic insulin resistance by regulating the ACE2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats. Our findings provide a better understanding of LXT for treatment of insulin resistance- and inflammation-associated liver injuries.

A CRISPR/Cas9-Mediated, Homology-Independent Tool Developed for Targeted Genome Integration in Yarrowia lipolytica.

Yarrowia lipolytica has been extensively used to produce essential chemicals and enzymes. As in most other eukaryotes, nonhomologous end joining (NHEJ) is the major repair pathway for DNA double-strand breaks in Y. lipolytica Although numerous studies have attempted to achieve targeted genome integration through homologous recombination (HR), this process requires the construction of homologous arms, which is time-consuming. This study aimed to develop a homology-independent and CRISPR/Cas9-mediated targeted genome integration tool in Y. lipolytica Through optimization of the cleavage efficiency of Cas9, targeted integration of a hyg fragment was achieved with 12.9% efficiency, which was further improved by manipulation of the fidelity of NHEJ repair, the cell cycle, and the integration sites. Thus, the targeted integration rate reached 55% through G1 phase synchronization. This tool was successfully applied for the rapid verification of intronic promoters and iterative integration of four genes in the pathway for canthaxanthin biosynthesis. This homology-independent integration tool does not require homologous templates and selection markers and achieves one-step targeted genome integration of the 8,417-bp DNA fragment, potentially replacing current HR-dependent genome-editing methods for Y. lipolyticaIMPORTANCE This study describes the development and optimization of a homology-independent targeted genome integration tool mediated by CRISPR/Cas9 in Yarrowia lipolytica This tool does not require the construction of homologous templates and can be used to rapidly verify genetic elements and to iteratively integrate multiple-gene pathways in Y. lipolytica This tool may serve as a potential supplement to current HR-dependent genome-editing methods for eukaryotes.

Antagonistic Interaction between Auxin and SA Signaling Pathways Regulates Bacterial Infection through Lateral Root in Arabidopsis.

Pathogen entry into host tissues is a critical and first step in infections. In plants, the lateral roots (LRs) are a potential entry and colonization site for pathogens. Here, using a GFP-labeled pathogenic bacterium Pseudomonas syringae pv. tomato strain DC3000 (Pto DC3000), we observe that virulent Pto DC3000 invades plants through emerged LRs in Arabidopsis. Pto DC3000 strongly induced LR formation, a process that was dependent on the AUXIN RESPONSE FACTOR7 (ARF7)/ARF19-LATERAL ORGAN BOUNDARIES-DOMAIN (LBD) regulatory module. We show that salicylic acid (SA) represses LR formation, and several mutants defective in SA signaling are also involved in Pto DC3000-induced LR development. Significantly, ARF7, a well-documented positive regulator of LR development, directly represses the transcription of PR1 and PR2 to promote LR development. This study indicates that ARF7-mediated auxin signaling antagonizes with SA signaling to control bacterial infection through the regulation of LR development.

Stable and Efficient Biosynthesis of 5-Aminolevulinic Acid Using Plasmid-Free Escherichia coli.

5-Aminolevulinic acid (5-ALA) is a key metabolic intermediate of the heme biosynthesis pathway, which has broad application prospects in agriculture and medicine. However, segregational instability of plasmid-based expression systems and low yield have hampered large-scale manufacture of 5-ALA. In this study, two important genes of the 5-ALA C5 biosynthesis pathway, hemA and hemL, were integrated into Escherichia coli MG1655 for chemically induced chromosomal evolution (CIChE). The highest hemA and hemL copy-number, 98 per genome, was obtained in CIChE strain MG136. The 5-ALA titer of this strain reached 2724 mg/L in optimized condition. Then, after undergoing adaptative evolution and the deletion of recA, strain MG136a ΔrecA::FRT could stably produce 4550 mg/L 5-ALA from glucose, 450 times the amount produced by hemA- hemL single copy strain MG1655-hemAL. This study constructed a plasmid-free E. coli strain for 5-ALA production, which will provide the basis for further manipulation of metabolic regulation and optimization of fermentation.

Visual presentation modality's superiority in the detection of concealed information: A comparison of the efficiencies of the P300-based Complex Trial Protocol in visual versus auditory modalities.

Some studies have shown a superiority of visual vs. auditory item presentation in the Complex Trial Protocol (CTP), which is a countermeasure-resistant version of the P300-based Concealed Information Test (CIT). But those studies used elaborately- rehearsed autobiographical information as stimuli, instead of incidentally-acquired crime-related information. Thus, the relative superiority of the visual as opposed to the auditory modality in detecting episodic crime-related information is still unknown. The present study also improved on the usual mock crime scenario by adding a mock disposal task between a mock theft and administration of a CTP test to increase stimulus saliency. In this CTP, the probe and the irrelevant items were presented visually or acoustically on alternating trials, while target and non-target stimuli were simultaneously presented in visual and auditory modalities. The results showed that the P300 amplitude differences of probe minus irrelevant items presented in the visual modality were significantly larger compared to the auditory modality, and the detection rate of the guilty participants was also significantly higher for the visual (14/16) versus auditory modality (5/16). These results suggest a superiority of visual vs. auditory presentation when a CTP is used to detect crime-related information in a mock crime scenario.

Homology-independent genome integration enables rapid library construction for enzyme expression and pathway optimization in Yarrowia lipolytica.

Yarrowia lipolytica is an important oleaginous industrial microorganism used to produce biofuels and other value-added compounds. Although several genetic engineering tools have been developed for Y. lipolytica, there is no efficient method for genomic integration of large DNA fragments. In addition, methods for constructing multigene expression libraries for biosynthetic pathway optimization are still lacking in Y. lipolytica. In this study, we demonstrate that multiple and large DNA fragments can be randomly and efficiently integrated into the genome of Y. lipolytica in a homology-independent manner. This homology-independent integration generates variation in the chromosomal locations of the inserted fragments and in gene copy numbers, resulting in the expression differences in the integrated genes or pathways. Because of these variations, gene expression libraries can be easily created through one-step integration. As a proof of concept, a LIP2 (producing lipase) expression library and a library of multiple genes in the ß-carotene biosynthetic pathway were constructed, and high-production strains were obtained through library screening. Our work demonstrates the potential of homology-independent genome integration for library construction, especially for multivariate modular libraries for metabolic pathways in Y. lipolytica, and will facilitate pathway optimization in metabolic engineering applications.

Inferior detection of information from collaborative versus individual crimes based on a P300 Concealed Information Test.

The present study used a P300-based Concealed Information Test (CIT) to detect individual and collaborative crimes and to explore whether or not the P300 index is effective in identifying collaborative crime members. Participants were divided into two groups to either steal a ring alone (individual group) or collaboratively with another companion participant (collaborative group) before taking the Complex Trial Protocol test that is regarded as an accurate version of the P300-based CIT. The ERP results revealed that both groups showed significantly larger P300s to probe (the ring) than to all irrelevant stimuli (other jewelery), but the P300 amplitude difference of probe stimulus versus irrelevant stimuli in the collaborative group was significantly less than that in the individual group. For the individual diagnosis, using P300 index, the detection rate was significantly inferior for collaborative crime than individual crime, probably related to weakness of collaborative encoding. The ROC curve comparisons showed the individual guilty was effectively discriminated from the simulated-innocent (AUC = .84) and from the collaborative guilty (AUC = .83), but the collaborative guilty was not discriminable from the simulated-innocent (AUC = .66). These findings suggest that collaborative encoding of crime-related information impacts the efficiency of the P300 index, and that the P300-based CIT is not applicable when used to identify collaborative crime perpetrators.

Efficacy of Retrobulbar Hyaluronidase Injection for Vision Loss Resulting from Hyaluronic Acid Filler Embolization.

BACKGROUND: Vision loss is a rare but serious complication of facial hyaluronic acid (HA) filler injection, for which there is no proven rescue therapy. Retrobulbar hyaluronidase injection is advocated by many plastic surgeons as an emergency treatment, but has not been carefully assessed for its efficacy. OBJECTIVES: To evaluate the efficacy of retrobulbar hyaluronidase injection as a rescue treatment for vision loss caused by HA filler embolization. METHODS: Patients with vision loss caused by HA filler embolization were treated with retrobulbar hyaluronidase injection. Their visual acuity and fundoscopic images before and after treatment were analyzed for efficacy assessment. RESULTS: One patient with branch retinal artery occlusion (BRAO), one patient with posterior ischemic optic neuropathy (PION), one patient with ophthalmic artery occlusion, and one patient with both BRAO and PION were treated with one or two retrobulbar injections of 1500 or 3000 units hyaluronidase. No patients demonstrated substantial retinal artery recanalization or vision acuity improvement after treatment. CONCLUSIONS: One or two retrobulbar injections of 1500 to 3000 IU hyaluronidase are unable to recanalize retinal artery occlusion or improve the visual outcome of patients who presented with vision loss caused by HA filler embolization at least four hours after onset. LEVEL OF EVIDENCE: 4.

Metaphorical mapping between raw-cooked food and strangeness-familiarity in Chinese culture.

Previous research has demonstrated metaphorical mappings between physical coldness-warmth and social distance-closeness. Since the concepts of interpersonal warmth are frequently expressed in terms of food-related words in Chinese, the present study sought to explore whether the concept of raw-cooked food could be unconsciously and automatically mapped onto strangeness-familiarity. After rating the nutritive value of raw or cooked foods, participants were presented with morphing movies in which their acquaintances gradually transformed into strangers or strangers gradually morphed into acquaintances, and were asked to stop the movies when the combined images became predominantly target faces. The results demonstrated that unconscious and automatic metaphorical mappings between raw-cooked food and strangeness-familiarity exist. This study provides a foundation for testing whether Chinese people can think about interpersonal familiarity using mental representations of raw-cooked food and supports cognitive metaphor theory from a crosslinguistic perspective.

Topoisomerase II-associated protein PAT1H1 is involved in the root stem cell niche maintenance in Arabidopsis thaliana.

KEY MESSAGE: PAT1H1, one of the homologues of Topoisomerase II-associated protein, is involved in the maintenance of root stem cell niche through the interaction with NINJA. The root stem cell niche, which possesses four mitotically inactive quiescent cells (QC) and the surrounding mitotically active stem cells, is critical for root development in Arabidopsis thaliana. However, the molecular regulation of the maintenance of root stem cell niche identity is still not fully understood. Here we show that one of the homologues of Topoisomerase II-associated protein, here named as PAT1H1, could regulate root stem cell niche identity. The pat1h1 mutant showed higher frequency of QC cell division and root distal stem cell (DSC) differentiation. With a high expression in roots, PAT1H1 was found to interact with the jasmonic acid (JA) signalling negative regulator Novel Interactor of JAZ (NINJA) and thus regulate root DSC niche identity. Consistent with the active QC cell division, which rarely occurs in wild-type controls, the pat1h1 mutant displayed higher expression of CYCB1 in the root stem cell niche. Together our data reveals that PAT1H1 maintains root stem cell niche stability through the interaction with NINJA and the regulation of cell division.