Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated Keratin 14 degradation.

Cutaneous squamous carcinoma is the second most common epithelial malignancy, associated with significant morbidity, mortality, and economic burden. However, the mechanisms underlying cSCC remain poorly understood. In this study, we identified TGM3 as a novel cSCC tumor suppressor that acts via the PI3K-AKT axis. RT-qPCR, IHC and western blotting were employed to assess TGM3 levels. TGM3-overexpression/knockdown cSCC cell lines were utilized to detect TGM3's impact on epithelial differentiation as well as tumor cell proliferation, migration, and invasion in vitro. Additionally, subcutaneous xenograft tumor models were employed to examine the effect of TGM3 knockdown on tumor growth in vivo. Finally, molecular and biochemical approaches were employed to gain insight into the tumor-suppressing mechanisms of TGM3. TGM3 expression was increased in well-differentiated cSCC tumors, whereas it was decreased in poor-differentiated cSCC tumors. Loss of TGM3 is associated with poor differentiation and a high recurrence rate in patients with cSCC. TGM3 exhibited tumor-suppressing activity by regulating cell proliferation, migration, and invasion both in vitro and in vivo. As a novel cSCC tumor differentiation marker, TGM3 expression was positively correlated with cell differentiation. In addition, our results demonstrated an interaction between TGM3 and KRT14 that aids in the degradation of KRT14. TGM3 deficiency disrupts keratinocytes differentiation, and ultimately leads to tumorigenesis. Furthermore, RNA-sequence analysis revealed that loss of TGM3 enhanced EMT via the PI3K-AKT signaling pathway. Deguelin, a PI3K-AKT inhibitor, blocked cSCC tumor growth induced by TGM3 knockdown in vivo. Taken together, TGM3 inhibits cSCC tumor growth via PI3K-AKT signaling, which could also serve as a tumor differentiation marker and a potential therapeutic target for cSCC. Proposed model depicted the mechanism by which TGM3 suppress cSCC development. TGM3 reduces the phosphorylation level of AKT and degrades KRT14. In the epithelial cell layer, TGM3 exhibits a characteristic pattern of increasing expression from bottom to top, while KRT14 and pAKT are the opposite. Loss of TGM3 leads to reduced degradation of KRT14 and activation of pAKT, disrupting keratinocyte differentiation, and eventually resulting in the occurrence of low-differentiated cSCC.

Feasibility of Using Magnetic Resonance Spectroscopy Test Biomarkers to Diagnose Alzheimer's Disease: Systematic Evaluation and Meta-Analysis.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, resulting in impairments in memory, cognition, decision-making, and social skills. Thus, accurate preclinical diagnosis of Alzheimer's disease is paramount. The identification of biomarkers for Alzheimer's disease through magnetic resonance spectroscopy (MRS) represents a novel adjunctive diagnostic approach. OBJECTIVE: This study conducted a meta-analysis of the diagnostic results of this technology to explore its feasibility and accuracy. METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched without restrictions, with the search period extending up to July 31, 2022. The search strategy employed a combination of subject headings and keywords. All retrieved documents underwent screening by two researchers, who selected them for meta-analysis. The included literature was analyzed using Review Manager 5.4 software, with corresponding bias maps, forest plots, and summary receiver operating characteristic (SROC) curves generated and analyzed. RESULTS: A total of 344 articles were retrieved initially, with 11 articles meeting the criteria for inclusion in the analysis. The analysis encompassed data from approximately 1766 patients. In the forest plot, both sensitivity (95% CI) and specificity (95% CI) approached 1. Examining the true positive rate, false positive rate, true negative rate, and false negative rate, all studies on the summary receiver operating characteristic (SROC) curve clustered in the upper left quadrant, suggesting a very high accuracy of biomarkers detected by MRS for diagnosing Alzheimer's disease. CONCLUSION: The detection of biomarkers by MRS demonstrates feasibility and high accuracy in diagnosing AD. This technology holds promise for widespread adoption in the clinical diagnosis of AD in the future.

Effects of Five Lipid Sources on Growth, Hematological Parameters, Immunity and Muscle Quality in Juvenile Largemouth Bass (Micropterus salmoides).

This study investigated the effects of fish oil (FO), soybean oil (SO), rapeseed oil (RO), peanut oil (PO) and lard oil (LO) on growth, immunity and muscle quality in juvenile largemouth bass. After 8 weeks, the results showed that FO and RO could increase weight gain and serum alkaline phosphatase and apelin values compared with LO (p < 0.05). Except lower crude lipid contents, higher amounts of n-3 polyunsaturated fatty acids (15.83% and 14.64%) were present in the dorsal muscle of the FO and RO groups. Meanwhile, FO and RO could heighten mRNA levels of immune defense molecules (lysozyme, hepcidin, and transforming growth factor ß1) compared with PO (p < 0.05). While SO could increase potential inflammatory risk via rising counts of white blood cells, platelets, neutrophils and monocytes, and mRNA levels of interleukins (IL-1ß, IL-8, IL-12 and IL-15), FO and RO could improve hardness, chewiness and springiness through increasing amounts of hydroxyproline, collagen and lysyl oxidase, and mRNA levels of collagen 1α2 and prolyl hydroxylase in the fish dorsal muscle. Moreover, FO and RO could improve firmness through increasing glycogen and glycogen synthase 1 levels when compared with LO (p < 0.05). Therefore, these results could provide dietary lipid source references during the feeding process of adult largemouth bass.

Effects of selenoprotein extracts from Cardamine hupingshanensis on growth, selenium metabolism, antioxidant capacity, immunity and intestinal health in largemouth bass Micropterus salmoides.

This study aimed to assess the impact of dietary selenoprotein extracts from Cardamine hupingshanensis (SePCH) on the growth, hematological parameters, selenium metabolism, immune responses, antioxidant capacities, inflammatory reactions and intestinal barrier functions in juvenile largemouth bass (Micropterus salmoides). The base diet was supplemented with four different concentrations of SePCH: 0.00, 0.30, 0.60 and 1.20 g/Kg (actual selenium contents: 0.37, 0.59, 0.84 and 1.30 mg/kg). These concentrations were used to formulate four isonitrogenous and isoenergetic diets for juvenile largemouth bass during a 60-day culture period. Adequate dietary SePCH (0.60 and 1.20 g/Kg) significantly increased weight gain and daily growth rate compared to the control groups (0.00 g/Kg). Furthermore, 0.60 and 1.20 g/Kg SePCH significantly enhanced amounts of white blood cells, red blood cells, platelets, lymphocytes and monocytes, and levels of hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin in the hemocytes. In addition, 0.60 and 1.20 g/Kg SePCH increased the mRNA expression levels of selenocysteine lyase, selenophosphate synthase 1, 15 kDa selenoprotein, selenoprotein T2, selenoprotein H, selenoprotein P and selenoprotein K in the fish liver and intestine compared to the controls. Adequate SePCH not only significantly elevated the activities of antioxidant enzymes (Total superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase), the levels of total antioxidant capacity and glutathione, while increased mRNA transcription levels of NF-E2-related factor 2, Cu/Zn-superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase. However, adequate SePCH significantly decreased levels of malondialdehyde and H2O2 and the mRNA expression levels of kelch-like ECH-associated protein 1a and kelch-like ECH-associated protein 1b in the fish liver and intestine compared to the controls. Meanwhile, adequate SePCH markedly enhanced the levels of immune factors (alkaline phosphatase, acid phosphatase, lysozyme, complement component 3, complement component 4 and immunoglobulin M) and innate immune-related genes (lysozyme, hepcidin, liver-expressed antimicrobial peptide 2, complement component 3 and complement component 4) in the fish liver and intestine compared to the controls. Adequate SePCH reduced the levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin 8, interleukin 1ß and interferon γ), while increasing transforming growth factor ß1 levels at both transcriptional and protein levels in the liver and intestine. The mRNA expression levels of mitogen-activated protein kinase 13 (MAPK 13), MAPK14 and nuclear factor kappa B p65 were significantly reduced in the liver and intestine of fish fed with 0.60 and 1.20 g/Kg SePCH compared to the controls. Histological sections also demonstrated that 0.60 and 1.20 g/Kg SePCH significantly increased intestinal villus height and villus width compared to the controls. Furthermore, the mRNA expression levels of tight junction proteins (zonula occludens-1, zonula occludens-3, Claudin-1, Claudin-3, Claudin-5, Claudin-11, Claudin-23 and Claudin-34) and Mucin-17 were significantly upregulated in the intestinal epithelial cells of 0.60 and 1.20 g/Kg SePCH groups compared to the controls. In conclusion, these results found that 0.60 and 1.20 g/Kg dietary SePCH can not only improve growth, hematological parameters, selenium metabolism, antioxidant capacities, enhance immune responses and intestinal functions, but also alleviate inflammatory responses. This information can serve as a useful reference for formulating feeds for largemouth bass.

Multiobjective optimization for flapping foil hydrodynamics with a multitask and multifidelity approach.

We develop a multitask and multifidelity Gaussian process (MMGP) model to accurately predict and optimize the multiobjective performance of a flapping foil while minimizing the cost of high-fidelity data. Through a comparison of three kernels, we have selected and applied the spectral mixture kernel and validated the robustness and effectiveness of a multiacquisition function. To effectively incorporate data with varying levels of fidelity, we have adopted a linear prior formula-based multifidelity framework. Additionally, Bayesian optimization with a multiacquisition function is adopted by the MMGP model to enable multitask active learning. The results unequivocally demonstrate that the MMGP model serves as a highly capable and efficient framework for effectively addressing the multiobjective challenges associated with flapping foils.

Selenium yeast improve growth, serum biochemical indices, metabolic ability, antioxidant capacity and immunity in black carp Mylopharyngodnpiceus.

This experiment was conducted to investigate the impacts of dietary selenium yeast (SeY) on the growth performance, fish body composition, metabolic ability, antioxidant capability, immunity and inflammatory responses in juvenile black carp (Mylopharyngodn piceus). The base diet was supplemented with 0.00, 0.30 and 0.60 g/kg SeY (0.04, 0.59 and 1.15 mg/kg of selenium) to form three isonitrogenous and isoenergetic diets for juvenile black carp with a 60-day. Adequate dietary SeY (0.30 and 0.60 g/kg) could significantly increase the weight gain (WG), special growth rate (SGR) compared to the SeY deficient groups (0.00 g/kg) (P < 0.05). Meanwhile, 0.30 and 0.60 g/kg SeY elevated the mRNA levels of selenoprotein T2 (SEPT2), selenoprotein H (SEPH), selenoprotein S (SEPS) and selenoprotein M (SEPM) in the liver and intestine compared with the SeY deficient groups (P < 0.05). Adequate dietary SeY could promote glucose catabolism and utilization through activating glucose transport (GLUT2), glycolysis (GCK, HK, PFK, PK, PDH), tricarboxylic acid cycle (ICDH and MDH), glycogen synthesis (LG, GCS and GBE) and IRS/PI3K/AKT signal pathway molecules (IRS2b, PI3Kc and AKT1) compared with the SeY deficient groups (P < 0.05). Similarly, adequate dietary SeY could improve lipid transport and triglycerides (TG) synthesis through increasing transcription amounts of CD36, GK, DGAT, ACC and FAS in the fish liver compared with the SeY deficient groups (P < 0.05). In addition, adequate SeY could markedly elevate activities of antioxidant enzymes (T-SOD, CAT, GR, GPX) and contents of T-AOC and GSH, while increased transcription amounts of Nrf2, Cu/Zn-SOD, CAT, and GPX in fish liver and intestine (P < 0.05). However, adequate SeY notably decreased contents of MDA, and the mRNA transcription levels of Keap1 in the intestine compared with the SeY deficient groups (P < 0.05). Adequate SeY markedly increased amounts or levels of the immune factors (ALP, ACP, LZM, C3, C4 and IgM) and the transcription levels of innate immune-related functional genes in the liver and intestine (LZM, C3 and C9) compared to the SeY deficient groups (P < 0.05). Moreover, adequate SeY could notably reduce levels of IL-8, IL-1ß, and IFN-γ and elevate TGF-1ß levels in fish intestine (P < 0.05). The transcription levels of MAPK13, MAPK14 and NF-κB p65 were notably reduced in fish intestine treated with 0.30 and 0.60 g/kg SeY (P < 0.05). In conclusion, these results suggested that 0.30 and 0.60 g/kg SeY could not only improve growth performance, increase Se, glucose and lipid metabolic abilities, enhance antioxidant capabilities and immune responses, but also alleviate inflammation, thereby supplying useful reference for producing artificial feeds in black carp.

Feasibility of Using Magnetic Resonance Spectroscopy Test Biomarkers to Diagnose Alzheimer's Disease: Systematic Evaluation and Meta-Analysis

Background: Alzheimer's disease (AD) is the leading cause of dementia, resulting in impairments in memory, cognition, decision-making, and social skills. Thus, accurate preclinical diagnosis of Alzheimer's disease is paramount. The identification of biomarkers for Alzheimer's disease through magnetic resonance spectroscopy (MRS) represents a novel adjunctive diagnostic approach.Objective: This study conducted a meta-analysis of the diagnostic results of this technology to explore its feasibility and accuracy.Methods: PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched without restrictions, with the search period extending up to July 31, 2022. The search strategy employed a combination of subject headings and keywords. All retrieved documents underwent screening by two researchers, who selected them for meta-analysis. The included literature was analyzed using Review Manager 5.4 software, with corresponding bias maps, forest plots, and summary receiver operating characteristic (SROC) curves generated and analyzed.Results: A total of 344 articles were retrieved initially, with 11 articles meeting the criteria for inclusion in the analysis. The analysis encompassed data from approximately 1766 patients. In the forest plot, both sensitivity (95% CI) and specificity (95% CI) approached 1. Examining the true positive rate, false positive rate, true negative rate, and false negative rate, all studies on the summary receiver operating characteristic (SROC) curve clustered in the upper left quadrant, suggesting a very high accuracy of biomarkers detected by MRS for diagnosing Alzheimer's disease.Conclusion: The detection of biomarkers by MRS demonstrates feasibility and high accuracy in diagnosing AD. This technology holds promise for widespread adoption in the clinical diagnosis of AD in the future. (AU)

Alzheimer's Disease and Cancer: Common Targets.

There is growing epidemiologic evidence of an inverse association between cancer and AD. In addition, both cell survival and death are regulated by the same signaling pathways, and their abnormal regulation may be implicated in the occurrence and development of cancer and AD. Research shows that there may be a common molecular mechanism between cancer and AD. This review will discuss the role of GSK3, DAPK1, PP2A, P53 and CB2R in the pathogenesis of cancer and AD and describe the current research status of drug development based on these targets.

Dietary cultured supernatant mixture of Cetobacterium somerae and Lactococcus lactis improved liver and gut health, and gut microbiota homeostasis of zebrafish fed with high-fat diet.

Postbiotics have the ability to improve host metabolic disorders and immunity. In order to explore whether the postbiotics SWFC (cultured supernatant mixture of Cetobacterium somerae and Lactococcus lactis) repaired the adverse effects caused by feeding of high-fat diet (HFD), zebrafish were selected as the experimental animal and fed for 6 weeks, with dietary HFD as the control group, and HFD containing 0.3 g/kg and 0.4 g/kg SWFC as the treatment groups. The results indicated that addition of SWFC in the diet at a level of 0.3 and 0.4 g/kg didn't affect the growth performance of zebrafish (P > 0.05). Supplementation of dietary SWFC0.3 relieved lipid metabolism disorders through significant increasing in the expression of pparα and cpt1, and decreasing the expression of cebpα, pparγ, acc1 and dgat-2 genes (P < 0.05). Moreover, the content of triacylglycerol was markedly lower in the liver of zebrafish grouped under SWFC0.3 (P < 0.05). Dietary SWFC0.3 also improved the antioxidant capacity via increasing the expression level of ho-1, sod and gstr genes, and significant inducing malondialdehyde content in the liver of zebrafish (P < 0.05). Besides, dietary SWFC0.3 also notably improved the expression level of lysozyme, c3a, defbl1 and defbl2 (P < 0.05). The expression level of pro-inflammatory factors (nf-κb, tnf-α, and il-1ß) were significantly decreased and the expression level of anti-inflammatory factor (il-10) was markedly increased in the postbiotics 0.3 g/kg group (P < 0.05). Feeding with SWFC0.3 supplemented diet for 6 weeks improved the homeostasis of gut microbiota and increased the survival rate of zebrafish after challenged with Aeromonus veronii Hm091 (P < 0.01). It was worth noting that the positive effect of dietary SWFC at a level of 0.3 g/kg was considerably better than that of 0.4 g/kg. This may imply that the effectiveness and use of postbiotics is limited by dosage.

Hyperpigmentation in an Elderly Patient with Atopic Dermatitis: A Quiz.

is missing (Quiz).

The expression profiling and clinical significance of a chronic pain-related gene IL1R1.

Chronic pain is a disease that existed during cancer treatment for a long time. It has been reported that interleukin (IL)-1 is involved in the inflammatory response during tumor development. IL1R1 and IL1R2 are members of the IL-1 receptor family of cytokine receptors. However, few studies have reported the role of chronic pain-related genes, IL1R1, in pan-cancer. In this study, 8 lumbar disc prolapse (LDP) patients and 8 controls with differentially expressed genes were investigated to find chronic pain-related genes. Then, IL1R1 was analyzed using the TCGA database. The clinical survival data from TCGA were used to analyze the prognostic value of IL1R1. This study further evaluated the relationship between IL1R1 and immune checkpoints, immune-activating genes, immunosuppressive genes, chemokines, and chemokine receptors. IL1R1 was expressed in varying degrees in most TCGA tumor types, indicating a better survival status. The expression of IL1R1 is closely related to T cell infiltration, immune checkpoints, immune-activating genes, immunosuppressive genes, chemokines, and chemokine receptors. The results show that IL1R1 is a kind of potential cancer biomarker. Coordination with other immune checkpoints IL1R1k may adjust the immune microenvironment, immunotherapy can be applied to the development of new targeted drugs.

Transcriptional variation in Babesia gibsoni (Wuhan isolate) between in vivo and in vitro cultures in blood stage.

BACKGROUND: Babesia gibsoni, the causative agent of canine babesiosis, belongs to the phylum Apicomplexa. The development of in vitro culture technology has driven research progress in various kinds of omics studies, including transcriptomic analysis of Plasmodium spp. between in vitro and in vivo environments, which has prompted the observation of diagnostic antigens and vaccine development. Nevertheless, no information on Babesia spp. could be obtained in this respect, which greatly hinders the further understanding of parasite growth and development in the blood stage. METHODS: In this study, considerable changes in the morphology and infectivity of continuous in vitro cultured B. gibsoni (Wuhan isolate) were observed compared to in vivo parasites. Based on these changes, B. gibsoni (Wuhan isolate) was collected from both in vivo and in vitro cultures, followed by total RNA extraction and Illumina transcriptome sequencing. The acquired differentially expressed genes (DEGs) were validated using qRT-PCR, and then functionally annotated through several databases. The gene with the greatest upregulation after in vitro culture was cloned from the genome of B. gibsoni (Wuhan isolate) and characterized by western blotting and indirect immunofluorescence assay for detecting the native form and cellular localization. RESULTS: Through laboratory cultivation, multiple forms of parasites were observed, and the infectivity of in vitro cultured parasites in dogs was found to be lower. Based on these changes, Illumina transcriptome sequencing was conducted, showing that 377 unigenes were upregulated and 334 unigenes were downregulated. Notably, an AP2 transcription factor family, essential for all developmental stages of parasites, was screened, and the transcriptional changes in these family members were tested. Thus, the novel AP2 transcription factor gene (BgAP2-M) with the highest upregulated expression after in vitro adaptation was selected. This gene comprises an open reading frame (ORF) of 1989 base pairs encoding a full-length protein of 662 amino acids. BgAP2-M contains one AP2 domain and one ACDC conserved domain, which may be involved in the nuclear biology of parasites. The prepared polyclonal antibodies against the BgAP2-M peptides further detected a native size of ~ 73 kDa and were localized to the nuclei of B. gibsoni. CONCLUSION: This study presents a thorough transcriptome analysis of B. gibsoni in vivo and in vitro for the first time, contributing to a detailed understanding of the effects of environmental changes on the growth and development of parasites in the blood stage. Moreover, it also provides a deeper investigation for the different members of the ApiAP2 transcription factor family as various life stage regulators in Babesia spp.

[Corrigendum] Roles of the H19/microRNA­675 axis in the proliferation and epithelial­mesenchymal transition of human cutaneous squamous cell carcinoma cells.

Following the publication of the above paper, a concerned reader drew to the authors' attention that, in Fig. 4C on p. 8, the 'Invasion, miR­675­inhibitor' data panel appeared to contain an overlapping section with the 'Invasion, mi­R675­inhibitor + pcDNA3.1­H19' data panel for the SCL1 cell line, such that the data were likely to have been derived from the same original source, even though they were intended to show the results from differently performed experiments. After having examined the original data, the authors also realized that the 'Inhibitor­NC' and 'miR­675­inhibitor' data panels showing the migration assay experiments for the A431 cell line in the same figure part had also inadvertently been derived from the same original source. After having been granted permission from the Editor of Oncology Reports to repeat the experiments shown in Fig. 4C, the revised version of Fig. 4, incorporating the new data for Fig. 4C, is shown on the next page. Note that these errors did not affect the overall conclusions reported in the study, and the repeated experiment yielded similar results to those obtained originally. The authors are grateful to the Editor for allowing them the opportunity to publish this corrigendum, and all the authors agree with the publication of this; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [Oncology Reports 45: 39, 2021; DOI: 10.3892/or.2021.7990].

Dietary Soybean Lecithin Improves Growth, Immunity, Antioxidant Capability and Intestinal Barrier Functions in Largemouth Bass Micropterus salmoides Juveniles.

This study evaluated the effects of dietary soybean lecithin (SBL) on the growth, haematological indices, immunities, antioxidant capabilities, and inflammatory and intestinal barrier functions because little information of dietary SBL could be obtained in juvenile largemouth bass (Micropterus salmoides). The fish were fed identical diets except for SBL added at 0, 2, 4 and 8%. It was found that 4 and 8% SBL significantly increased fish weight gain and daily growth rate (p < 0.05), while 4% SBL was optimal for enhancing RBC, HGB, PLT, MCV, MCH, WBC and MON in blood, and ALB and ALP in serum (p < 0.05). SBL (4%) also significantly elevated the antioxidant enzymes activities of T-SOD, CAT, GR, GPx, GST and T-AOC and GSH contents; increased mRNA transcription levels of Nrf2, Cu/Zn-SOD, CAT, GR, GST3 and GPx3; and decreased MDA contents. Keap1a and Keap1b levels were markedly down-regulated (p < 0.05). SBL (4%) significantly enhanced levels of the immune factors (ACP, LZM and C3) and the mRNA expression levels of innate immune-related genes (C3, C4, CFD, HEPC and MHC-I) compared with the control groups (0%) (p < 0.05). SBL (4%) significantly increased IgM and T-NOS in the intestine (p < 0.05) and significantly decreased levels of TNF-α, IL-8, IL-1ß and IFN-γ and increased TGF-ß1 at both transcription and protein levels in the liver and intestine (p < 0.05). The mRNA expression levels of MAPK13, MAPK14 and NF-κB P65 were significantly decreased in the intestine in the 4% SBL groups (p < 0.05). Histological sections also demonstrated that 4% SBL protected intestinal morphological structures compared with controls. This included increased intestinal villus height and muscular thickness (p < 0.05). Furthermore, the mRNA expression levels of the intestinal epithelial cell tight junction proteins (TJs) (ZO-1, claudin-3, claudin-4, claudin-5, claudin-23 and claudin-34) and mucin-5AC were significantly up-regulated in the 4% SBL groups compared with the controls (p < 0.05). In conclusion, these results suggested that 4% dietary SBL could not only improve growth, haematological indices, antioxidant capabilities, immune responses and intestinal functions, but also alleviate inflammatory responses, thereby providing reference information for the feed formulations in cultured largemouth bass.

Dual fluorination of polymer electrolyte and conversion-type cathode for high-capacity all-solid-state lithium metal batteries.

All-solid-state batteries are appealing electrochemical energy storage devices because of their high energy content and safety. However, their practical development is hindered by inadequate cycling performances due to poor reaction reversibility, electrolyte thickening and electrode passivation. Here, to circumvent these issues, we propose a fluorination strategy for the positive electrode and solid polymeric electrolyte. We develop thin laminated all-solid-state Li||FeF3 lab-scale cells capable of delivering an initial specific discharge capacity of about 600 mAh/g at 700 mA/g and a final capacity of about 200 mAh/g after 900 cycles at 60 °C. We demonstrate that the polymer electrolyte containing AlF3 particles enables a Li-ion transference number of 0.67 at 60 °C. The fluorinated polymeric solid electrolyte favours the formation of ionically conductive components in the Li metal electrode's solid electrolyte interphase, also hindering dendritic growth. Furthermore, the F-rich solid electrolyte facilitates the Li-ion storage reversibility of the FeF3-based positive electrode and decreases the interfacial resistances and polarizations at both electrodes.

Nuclease treatment enhanced the ameliorative effect of yeast culture on epidermal mucus, hepatic lipid metabolism, inflammation response and gut microbiota in high-fat diet-fed zebrafish.

As a functional feed additive, yeast cultures are rich in nucleotides, and adding extra nuclease can significantly increase the content of nucleotides in yeast culture. In this experiment, the effects on growth, epidermal mucus, liver and intestinal health of zebrafish were evaluated by supplementing the yeast culture or nuclease-treated yeast culture with a high-fat diet (HFD). One-month-old zebrafish were fed four diets: normal diet (NORM), HFD, yeast culture diet (YC), and nuclease-treated yeast culture diet (YC (N)) for three weeks. Results showed that the complement 4 activity of the epidermal mucus in YC (N) group was significantly higher than those in HFD and YC groups (P < 0.05). The YC and YC (N) significantly reduced the content of hepatic triglyceride caused by HFD (P < 0.05). Moreover, compared with the YC group, the YC (N) significantly increased the expression of lipolysis genes, such as PPARα, PGC1α, ACOX3 (P < 0.05). Compared with the YC group, the YC (N) group significantly increased the expression of liver pro-inflammatory factors TNFα, IL-6, IL-1ß and anti-inflammatory factors TGFß, IL-10 (P < 0.05). The diet YC and YC (N) significantly improved the height of the intestinal villus (P < 0.05). Compared with the HFD group, the YC (N) group significantly increased the expression of intestinal pro-inflammatory factors TNFα, IL-6 and anti-inflammatory factors TGFß, IL-10 (P < 0.05). The YC (N) group significantly decreased the abundance of intestinal Proteobacteria and Acinetobacter, and increased the abundance of intestinal Actinobacteria, Mycobacterium and Rhodobacter (P < 0.05). In conclusion, compared with the supplement of yeast culture, nuclease treated yeast culture can further alleviate the adverse effects of HFD on liver and intestinal health, and be used as feed additives for the nutritional and immune regulation of fish.

Stroke outcome of early antiplatelet in post-thrombolysis haemorrhagic infarction.

BACKGROUND AND PURPOSE: Initiation of early antiplatelet (EA) therapy after acute ischaemic stroke (AIS) is essential. We aimed to investigate the safety and effectiveness of EA therapy in patients who had an AIS with haemorrhagic infarction (HI) after intravenous thrombolysis (IVT). METHODS: Based on a multicentre stroke registry database, patients who had an AIS with post-thrombolysis HI at 24 hours were identified. EA users and non-EA users were defined as patients with HI who received or did not receive antiplatelet therapy between 24 and 48 hours after IVT. Primary outcome was favourable outcome defined as modified Rankin Scale scores 0-2 at 3 months. Secondary outcomes were early neurological deterioration (END) and haemorrhagic transformation expansion. RESULTS: A total of 842 patients with HI were identified from 24 061 thrombolytic patients within 4.5 hours, and 341 (40.5%) received EA therapy. EA users were more likely to have a favourable outcome (55.7% vs 39.5%, OR 1.565; 95% CI 1.122 to 2.182; p=0.008) and lower rate of END (12.6% vs 21.4%, OR 0.585; 95% CI 0.391 to 0.875; p=0.009) compared with non-EA users. EA therapy was not associated with haemorrhagic transformation expansion (p=0.125). After propensity score matching, EA therapy was still independently associated with favourable outcome (54.3% vs 46.3%, OR 1.495; 95% CI 1.031 to 2.167; p=0.038) and lower risk of END (13.5% vs 21.2%, OR 0.544; 95% CI 0.350 to 0.845; p=0.007). CONCLUSIONS: Antiplatelet therapy can be safely used between 24 and 48 hours when HI occurs after IVT, and such therapy is associated with reduced risk of END and improved neurological outcome in patients who had an AIS.

Safety of Recanalization Therapy in Acute Ischemic Stroke Patients on Direct Oral Anticoagulant Therapy: An Updated Systematic Review and Meta-Analysis.

This review provides an updated assessment of the safety of recanalization therapy for Acute Ischemic Stroke (AIS) patients receiving direct oral anticoagulants (DOAC) therapy. We checked the literature for published observational from 1st January 1950 to 31st March 2021. The rate of symptomatic intracerebral hemorrhage (sICH), arterial recanalization rate, good functional recovery, and mortality at 3 months were investigated, and data were expressed as Risk ratio (RR) with a 95% confidence interval (CI). Publication bias, sensitivity analysis, and meta-regression analyses were conducted utilizing STATA software. 17 articles [14 for endovascular therapy (EVT) and 3 intravenous thrombolysis for (IVT)] were finally included in the review. AIS patients with DOAC therapy showed a decreased rate of sICH (RR = 0.85, 95% CI = 0.72 to 1.00, P = 0.04), and lower probability of good functional recovery at three months (RR = 0.79, 95% CI = 0.73 to 0.85, P < 0.001) than patients without anticoagulation therapy post EVT. However, no significant differences in sICH rates in AIS patients with DOAC therapy after IVT (RR = 0.87, 95% CI = 0.48 to 1.58, P = 0.64) were observed. AIS patients not prescribed DOAC after EVT had a higher mortality risk (RR = 1.29, 95% CI = 1.15-1.44, P < 0.001). Patients with AIS on DOAC therapy were found to have a lower incidence of sICH following EVT. However, no evidence of an increased bleeding risk in patients previously treated with DOAC after IVT was observed. Therefore, more detailed studies with biological data to monitor compliance and details on the size and etiology/severity of the incident ischemic lesion is needed.