A nomogram for predicting the risk of preeclampsia in women with intrahepatic cholestasis of pregnancy based on prenatal monitoring time: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: Intrahepatic cholestasis of pregnancy (ICP) is a special liver disease during pregnancy, characterized by abnormal bile acid metabolism. However, there is no consensus on how to group women with ICP based on the time of diagnosis worldwide. This study aimed to adopt a new grouping model of women with ICP, and the time from diagnosis to delivery was defined as the monitoring period. METHODS: This retrospective real-world data study was conducted across multiple centers and included 3172 women with ICP. The study first evaluated the significant difference in medication and nonmedication during different monitoring times. The least absolute shrinkage and selection operator (LASSO) model was then used to screen nine risk factors based on the predictors. The model's discrimination, clinical usefulness, and calibration were assessed using the area under the receiver operating characteristic (ROC) curve, decision curve, and calibration analysis. RESULTS: The incidence of preeclampsia risk in ICP patients without drug intervention increased with the extension of the monitoring period. However, the risk of preeclampsia decreased in ICP patients treated with ursodeoxycholic acid. A predictive nomogram and risk score model was developed based on nine risk factors. The area under the ROC curve of the nomogram was 0.765 [95% confidence interval (CI): 0.724-0.807] and 0.812 (95% CI: 0.736-0.889) for the validation cohort. CONCLUSIONS: This study found that a longer ICP monitoring period could lead to adverse pregnancy outcomes in the absence of drug intervention, especially preeclampsia. A predictive nomogram and risk score model was developed to better manage ICP patients, maintain pregnancy to term delivery, and minimize the risk of severe adverse maternal and fetal outcomes.

Role of inflammatory lipid and fatty acid metabolic abnormalities induced by plastic additives exposure in childhood asthma.

Lipid metabolism play an essential role in occurrence and development of asthma, and it can be disturbed by phthalate esters (PAEs) and organophosphate flame retardants (OPFRs). As a chronic inflammatory respiratory disease, the occurrence risk of childhood asthma is increased by PAEs and OPFRs exposure, but it remains not entirely clear how PAEs and OPFRs contribute the onset and progress of the disease. We have profiled the serum levels of PAEs and OPFRs congeners by liquid chromatography coupled with mass spectrometry, and its relationships with the dysregulation of lipid metabolism in asthmatic, bronchitic (acute inflammation) and healthy (non-inflammation) children. Eight PAEs and nine OPFRs congeners were found in the serum of children (1 - 5 years old) from Shenzhen, and their total median levels were 615.16 ng/mL and 17.06 ng/mL, respectively. Moreover, the serum levels of mono-methyl phthalate (MMP), tri-propyl phosphate (TPP) and tri-n-butyl phosphate (TNBP) were significant higher in asthmatic children than in healthy and bronchitic children as control. Thirty-one characteristic lipids and fatty acids of asthma were screened by machine-learning random forest model based on serum lipidome data, and the alterations of inflammatory characteristic lipids and fatty acids including palmitic acids, 12,13-DiHODE, 14,21-DiHDHA, prostaglandin D2 and LysoPA(18:2) showed significant correlated with high serum levels of MMP, TPP and TNBP. These results imply PAEs and OPFRs promote the occurrence of childhood asthma via disrupting inflammatory lipid and fatty acid metabolism, and provide a novel sight for better understanding the effects of plastic additives on childhood asthma.

Safety of Sonazoid in Assisting High-Intensity Focused Ultrasound Ablation Therapy for Advanced Liver Malignant Lesions: A Single-Arm Clinical Study.

OBJECTIVE: The aim of the study described here was to evaluate the safety of Sonazoid-assisted high-intensity focused ultrasound (HIFU) in the treatment of advanced malignant liver lesions. METHODS: A single-arm study was designed to enroll participants who were diagnosed with advanced primary liver cancer or liver metastases and proposed to receive Sonazoid assistance during HIFU treatment. Serological examination was conducted within 1 wk, and side effects in each patient were monitored for 1 mo. To evaluate therapeutic efficacy, the contrast-enhanced magnetic resonance imaging was performed 1 mo after treatment, and short-term follow-up was conducted a year later. RESULTS: A total of 17 participants (12 male, 5 female) with an average age of 58 y (range: 46-73 y) were enrolled, including 11 patients with hepatocellular carcinoma, 2 patients with hepatic metastasis and 4 patients with cholangiocarcinoma. The total volume of tumor mass was 111.82 (11.01-272.30) cm3. The average total ablation time for a patient was 2021 ± 1030 s, and the energy efficiency factor was 5979.7 (3108.0, 45634.5) J/cm3. Immediately after HIFU treatment, 1 patient (5.9%) achieved complete response (CR), 4 patients (23.5%) had a moderate response, 8 patients (47.1%) had partial reperfusion and 4 patients (23.5%) had stable disease (SD). The average ablation rate for all the tumors was 51.5 ± 26.7%. The level of glutamic-pyruvic transaminase (ALT) was mildly increased in 71.6% (12/17) of patients after HIFU therapy. Mean ALT values before and after treatment were 22 (14, 35) U/L and 36 (25, 41) U/L, respectively (Z = 1.947, p = 0.051). Mild or obvious edema in skin and subcutaneous soft tissues were observed in 76.5% of patients, but no serious side effects were found. Twelve months after treatment, the follow-up results revealed that 1 patient (5.8%) achieved a CR, 8 patients (47.1%) had SD and 8 patients (47.1%) had progressive disease. The estimated median time to progression was 11 mo after treatment, with a 95% confidence interval of 6, 11 for all involved patients. CONCLUSION: Use of Sonazoid is safe and feasible for improving HIFU ablation efficiency during the treatment of advanced malignant liver lesions. The therapeutic efficacy of Sonazoid-assisted HIFU needs to be explored in additional controlled clinical investigations.

Saponins derived from Gynostemma pentaphyllum regulate triglyceride and cholesterol metabolism and the mechanisms: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) can be used for both medicinal and tea and has lipid-lowering properties. Modern research has shown that its main bioactive components are flavonoids and saponins. It has many beneficial effects such as hypolipidemic, anti-cancer, cardioprotective, hepatoprotective, neuroprotective, anti-diabetic and anti-inflammatory. AIMS OF THE REVIEW: This review aimed to summarize its anti-glycolipid metabolic models and mechanisms are reviewed to facilitate a deeper understanding of the mechanism in lowering lipids. MATERIALS AND METHODS: Information related to lipid lowering in G. pentaphyllum was collated by reviewing the relevant literature in the PubMed database from 1985 to 2023. RESULTS: Only 101 G. pentaphyllum compounds have been initially explored for their hypolipidemic activity. There are cell models, animal models and human subjects for lipid-lowering of it. It reduced triglyceride level via PPAR/UCP-1/PGC-1α/PRDM16 and (SREBP-1c)-ACC/FAS-CPT1 signal pathways. Cholesterol-lowering effects via (SREBP-2)-HMGCR, PCSK9-LDLR and bile acid biosynthetic pathways. Activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) is a key factor in the regulation of glycolipid metabolism in G. pentaphyllum. Other pathways of action of G. pentaphyllum in regulating glucolipid metabolism are also discussed in this paper. CONCLUSION: To date, more than 328 saponins have been isolated and identified in Gynostemma. Further studies on these components, including molecular mechanisms and in vivo metabolic regulation, need to be further confirmed. G. pentaphyllum has the potential to be developed into drugs or functional foods, but further research is needed.

Lake plastisphere as a new biotope in the Anthropocene: Potential pathogen colonization and distinct microbial functionality.

The not-homogenous microplastics (MPs) distribution in freshwaters results in distinct microbial communities. Yet knowledge regarding plastisphere in metabolic pathways and element cycling behaviors remains limited. In this study, we collected MPs from 15 sampling sites in the Taihu Lake in China, and found that MPs were widely distributed in this freshwater lake, and dominantly composed of fibrous polyethylene terephthalate. Based on the metagenomic analysis, we found that MPs were colonized by Bacteroidia, Alpha-Proteobacteria, and Bacilli as a filter, but depleted in Verrucomicrobiae. Potential pathogens of plant eudicots and monocots were significantly enriched in plastisphere. Predicted functional profiles involved in the metabolism of other amino acids, biosynthesis of other secondary metabolites, and glycan biosynthesis and metabolism were overrepresented in plastisphere. Regarding elemental cycling, functional genes related to nitrogen fixation and nitrification showed 39.6% and 67.5% decline in plastisphere, whereas the genes involved in denitrification and nitrate reduction were significantly enriched. For sulfur cycles, the plastisphere exhibited higher sulfate reduction and sulfur oxidation system activities. Additionally, the taxonomic compositions and predicted functions in the plastispheres were mainly driven by the stochastic processes, while the deterministic processes were more important for the planktonic communities. The distinctions in the microbial composition, the predicted functionality, and the underly mechanisms between plastisphere and planktonic communities illustrated the unique ecology of the new anthropogenic-related plastisphere ecosystems.

Optimization of a QuEChERS-LC-MS/MS method for 51 pesticide residues followed by determination of the residue levels and dietary intake risk assessment in foodstuffs.

A modified QuEChERS purification-liquid chromatography-tandem mass spectrometry method has been developed to determine 51 pesticide residues with newly established maximum residue limits (MRLs) in foodstuffs. Samples were extracted with acetonitrile under citrate-buffered conditions and purified using a modified QuEChERS method employing hydroxylated MWCNTs, SAX, and C18. The limits of quantification ranged from 0.2 to 9.8 µg/kg. Recoveries in ten different foodstuffs ranged from 70.2% to 117.9%, with relative standard deviations between 2.3% and 19.9% at three spiking levels. This method was applied to analyze 352 market samples, detecting 14 pesticides in 97 samples. Notably, Afidopyropen, cyantraniliprole, and fluxapyroxad residues in vegetables exhibited a consistent pattern of higher levels in the spring and winter and lower levels in the summer and autumn. Moreover, the risk assessments for acute and chronic dietary exposure to the 14 detected pesticides indicated that the %ADI and %ARfD were well below 100%.

Multi-omics revealed the mechanisms of Codonopsis pilosula aqueous extract in improving UC through blocking abnormal activation of PI3K/Akt signaling pathway.

ETHNOPHARMACOLOGICALRELEVANCE: Codonopsis pilosula (DS), a traditional Chinese medicine, had been used to regulate the immune, digestive and circulatory systems of the human, as well as protect the gastrointestinal tract, improve lung function. AIM OF THE STUDY: The aim of study was to explore the effects and mechanism of Codonopsis pilosula aqueous extract (DS) intervention in improving ulcerative colitis (UC). MATERIALS AND METHODS: UC model rats were established using combination of TNBS and ethanol. Tissue samples were collected for transcriptome and metabolomics analysis. Network pharmacology was performed on DS to identify bioactive compounds. Western blot was used to detect the key proteins involved in UC pathogenesis and PI3K/AKT pathways. RESULTS: DS exerted the preventive and therapeutic effects in improving UC via inhibiting abnormal inflammatory responses and promoting antioxidant capacity. Levels of intestinal barrier, oxidative stress and inflammatory mediators were improved to nearly normal level in vivo by DS. Metabolome profiles showed that DS could restore the metabolic disorders associated with the UC pathogenesis. Further transcriptome results showed that DS mainly alleviate UC through inhibiting PI3K/Akt signaling pathway, and various related genes that dramatically expressed in UC Model rats were downregulated by DS. Typically, network pharmacology analysis identified that Glycitein was the hub compounds that involved in the mechanism of DS in improving UC. CONCLUSIONS: The results show that Codonopsis pilosula (DS) was an potential excellent material in treating of UC depending on its suitable concentration. Possible therapeutic mechanisms of the DS involved in mitigating colonal inflammation, restoring metabolic disorders, promoting antioxidant capacity, and especially blocking the activation of PI3K/Akt pathway.

Bioaccessibility of docosahexaenoic acid in naturally and artificially enriched milk.

This study aimed to compare the bioaccessibility of docosahexaenoic acid (DHA) in naturally and artificially enriched milk and investigate the potential mechanisms involved. The results indicated that the DHA in naturally enriched milk (NEM) had a higher bioaccessibility (76.9 %) and a lower digestive loss rate (18.1 %) compared to artificially enriched milk (ArEM). Moreover, NEM contained a higher proportion of DHA-containing glycerophospholipids and sn-2 DHA, with fewer long-chain fatty acids and more saturated fatty acids adjacent to DHA in the same lipid molecule. During simulated intestinal digestion, NEM had a higher free fatty acid release and lipid digestion rate than ArEM. These findings suggested that the bioaccessibility of endogenous DHA in milk was superior to that of externally added DHA due to its more easily digestible and absorbable chemical binding form and lower digestive loss rate. The easy digestibility of milk lipids in NEM also contributed to its high DHA bioaccessibility.

Fluorescent composite based on peptide nanotubes activating coumarin 6 for sensitive detection of new coccine in food samples.

New coccine (NC), as a kind of common colorant, has been frequently used in our daily life. Herein, the fluorescent composite (PNTs@C6) prepared by the hydrophobic non-covalent interaction between peptide nanotubes and coumarin 6 (C6) was designed for the determination of NC. Due to the activation of C6 by peptide nanotubes, the composite exhibits strong green fluorescence emission, which can be selectively quenched by NC through the inner filter effect. Therefore, a new fluorescent method based on the PNTs@C6 composite for NC detection was constructed. Under optimal conditions, the fluorescence quenching of the sensor exhibits a good linear relationship with the concentration of NC in the range of 0.01-10 µM and the limit of detection is 3.6 nM. Furthermore, the strategy shows simplicity, rapid response and high selectivity and has been successfully applied to the detection of NC in food samples.

Pandemics uncertainty and informational globalization in CEE countries: The role of innovation diffusion.

The Covid-19 pandemic has dramatically changed how information is shared and processed worldwide. The COVID-19 pandemic has profoundly affected the globalization of information, causing shifts in communication, information dissemination, and technology. This paper investigates the impact of pandemics-related uncertainty on the index of de facto informational globalization (the measure based on high-technology exports, international patents, and used internet bandwidth). The paper uses the panel dataset of 18 Central and Eastern European (CEE) countries from 1990 to 2020. The results indicate that pandemics-related uncertainty negatively affects the informational globalization level in the CEE economies. The findings are robust in utilizing different estimation techniques and considering NATO member CEE countries.

Disclosing Potential Therapeutic Targets Associated With Osimertinib Resistance in the Non-small Cell Lung Cancer Cell Line H1975.

BACKGROUND/AIM: Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is a highly effective and valuable treatment option for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations, such as T790M. However, acquired resistance ultimately limits its clinical application. In this study, we aimed to identify potential targets for overcoming osimertinib resistance. MATERIALS AND METHODS: The H1975/OSI cell line was induced in vitro through intermittent induction. Cell activity was measured using a cell counting kit-8 assay. Uni-omics and multi-omics analyses were conducted on the transcriptomic and proteomic (4D label-free) expression profiles, which involved differential expression analysis, GO functional annotation and KEGG pathway enrichment analysis, as well as correlation analysis of transcription factors and PPI network. RESULTS: H1975/OSI cells showed resistance towards osimertinib with IC50 values approximately 5.25-fold higher than H1975 cells. A total of 2519 genes were found to be differentially expressed genes (DEGs) and 1533 proteins were found to be differentially abundant proteins (DAPs). Furthermore, 147 genes that were differentially expressed at both the transcription and protein levels (TPGs) were identified as being differentially expressed in both the transcriptome and proteome. It was revealed that many pathways related to the structure and function of ribosomes, as well as metabolites, were altered. The highest connectivity genes of 147 TPGs included NOP56, DDX21, PDCD11, CCNB1, and TOP2A. The hub genes of the transcriptional regulatory network included DDX21, KPNA2, DDX5, BRCA1, LMNB1, and HIF1A. CONCLUSION: Collectively, our high-throughput analysis uncovered functional properties that interacted with gene signatures of H1975/OSI cells, and highlighted certain pathways and eleven hub genes that may be the potential targets for improving clinical osimertinib resistance.

ABIN1 (Q478) is Required to Prevent Hematopoietic Deficiencies through Regulating Type I IFNs Expression.

A20-binding inhibitor of NF-κB activation (ABIN1) is a polyubiquitin-binding protein that regulates cell death and immune responses. Although Abin1 is located on chromosome 5q in the region commonly deleted in patients with 5q minus syndrome, the most distinct of the myelodysplastic syndromes (MDSs), the precise role of ABIN1 in MDSs remains unknown. In this study, mice with a mutation disrupting the polyubiquitin-binding site (Abin1Q478H/Q478H ) is generated. These mice develop MDS-like diseases characterized by anemia, thrombocytopenia, and megakaryocyte dysplasia. Extramedullary hematopoiesis and bone marrow failure are also observed in Abin1Q478H/Q478H mice. Although Abin1Q478H/Q478H cells are sensitive to RIPK1 kinase-RIPK3-MLKL-dependent necroptosis, only anemia and splenomegaly are alleviated by RIPK3 deficiency but not by MLKL deficiency or the RIPK1 kinase-dead mutation. This indicates that the necroptosis-independent function of RIPK3 is critical for anemia development in Abin1Q478H/Q478H mice. Notably, Abin1Q478H/Q478H mice exhibit higher levels of type I interferon (IFN-I) expression in bone marrow cells compared towild-type mice. Consistently, blocking type I IFN signaling through the co-deletion of Ifnar1 greatly ameliorated anemia, thrombocytopenia, and splenomegaly in Abin1Q478H/Q478H mice. Together, these results demonstrates that ABIN1(Q478) prevents the development of hematopoietic deficiencies by regulating type I IFN expression.

Design, Synthesis, and Biological Investigations of Novel Carbamoylguanidinyl Nitrobenzoxadiazoles against Chitinolytic Enzymes.

Chitinase has been identified as an important target for insecticides. In this study, a series of novel chitinase inhibitors was designed and synthesized with nitrobenzoxadiazoles. Compound 8d, which contains the N-methylcarbamoylguanidinyl, exhibited high enzyme inhibitory activity and achieved nanomolar inhibition against OfChtI (IC50 = 12.3 nM). Delightfully, it was also found to possess significant inhibitory activity against OfHex1 (IC50 = 1.76 µM). The computational simulation results indicated that compound 8d interacted with OfChtI and OfHex1 in similar modes through hydrogen bonds and hydrophobic and π-π interactions. Insecticidal activity studies revealed that compound 8d showed high mortality against the Lepidoptera Plutella xylostella (mortality rate = 81%) at 200 mg/L. Toxicity studies indicated that compound 8d exhibited negligible toxicity to the natural enemy Trichogramma ostriniae. These results indicate that compound 8d may be a promising candidate for the development of environmentally friendly chitinase inhibitors. Moreover, this study provides a new angle for the design of innovative inhibitors of chitinolytic enzymes.

Comparative analysis of algorithm-guided treatment and predefined duration treatment programmes for depression: exploring cost-effectiveness using routine care data.

BACKGROUND: More knowledge on the cost-effectiveness of various depression treatment programmes can promote efficient treatment allocation and improve the quality of depression care. OBJECTIVE: This study aims to compare the real-world cost-effectiveness of an algorithm-guided programme focused on remission to a predefined duration, patient preference-centred treatment programme focused on response using routine care data. METHODS: A naturalistic study (n=6295 in the raw dataset) was used to compare the costs and outcomes of two programmes in terms of quality-adjusted life years (QALY) and depression-free days (DFD). Analyses were performed from a healthcare system perspective over a 2-year time horizon. Incremental cost-effectiveness ratios were calculated, and the uncertainty of results was assessed using bootstrapping and sensitivity analysis. FINDINGS: The algorithm-guided treatment programme per client yielded more DFDs (12) and more QALYs (0.013) at a higher cost (€3070) than the predefined duration treatment programme. The incremental cost-effectiveness ratios (ICERs) were around €256/DFD and €236 154/QALY for the algorithm guided compared with the predefined duration treatment programme. At a threshold value of €50 000/QALY gained, the programme had a probability of <10% of being considered cost-effective. Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: The algorithm-guided programme led to larger health gains than the predefined duration treatment programme, but it was considerably more expensive, and hence not cost-effective at current Dutch thresholds. Depending on the preferences and budgets available, each programme has its own benefits. CLINICAL IMPLICATION: This study provides valuable information to decision-makers for optimising treatment allocation and enhancing quality of care cost-effectively.

[High-throughput screening of 54 alternative plasticizers in sesame oil using gas chromatography-quadrupole time-of-flight mass spectrometry].

Restrictions on the use of phthalates have led to the wide use of alternative plasticizers (APs) such as organophosphate, adipate, citrate, and sebacate. However, because plasticizers combine with polymers in plastic products via unstable noncovalent bonds, they can easily migrate out of these products, causing environmental pollution. In particular, their migration out of food packaging, containers, and other food-contact materials and into food has raised great concerns. Toxicological studies have shown that APs contain potentially toxic substances that can affect endocrine functions and cause neurotoxicity, genotoxicity, and other adverse effects. Thus, their potential risks to food should not be underestimated. Sesame oil is a necessity in daily cooking. The results of risk monitoring in recent years have indicated that sesame oil often contains phthalates in excess of the standard limits. However, the potential risks of APs in sesame oil have not yet been reported. Some common detection methods for APs include gas chromatography-mass spectrometry, gas chromatography-triple quadrupole mass spectrometry, and liquid chromatography-triple quadrupole mass spectrometry. Unfortunately, these methods use low-resolution mass spectrometry and are limited by the resolution, scan rate, and analysis mode. Gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF/MS) has the advantages of high resolution, sensitivity, and analysis speed. In full-scan mode, GC-Q-TOF/MS can accurately collect the full-spectrum mass number of target compounds with low content levels in complex substrates, thereby realizing efficient screening and quantitative analysis. It shows outstanding advantages in the trace analysis of pesticide residues and pollutants. Furthermore, it features strong qualitative and high screening abilities. Establishment of a personal compound database and library (PCDL) addresses limitations in the number of compounds that can be measured and enables the rapid identification of targets without the use of standard products. In addition, increasing the number of targets for synchronous screening enables the retrospective analysis of new targets. In this study, a method based on GC-Q-TOF/MS was developed for the determination of 54 APs in sesame oil. The samples were extracted with acetonitrile and purified using a PSA/silica solid-phase extraction column. The mass-spectral information of the samples was then collected by GC-Q-TOF/MS in full-scan mode, and the 54 APs were searched using an established high-resolution mass-spectrum database to simultaneously achieve the broad-spectrum screening, qualitative identification, and quantitative analysis of multiple targets. The effects of different extraction solvents and purification methods on sample extraction and purification were compared. The accuracy of the screening results was improved by optimizing the GC-separation conditions, quality-extraction window, retention-time deviation, and other screening parameters. The screening detection limits (SDLs) of the 54 APs ranged from 0.01 to 0.02 mg/kg; specifically, the SDL of 41 compounds was 0.01 mg/kg and that of 13 compounds were 0.02 mg/kg. The limits of quantification were in the range of 0.02-0.04 mg/kg. A total of 80 sesame-oil samples were rapidly screened using this method under optimal conditions. Five APs were identified from the 80 sesame-oil samples and quantitatively analyzed using the matrix-matched external-standard method. The results of this quantitative methodology showed that the five APs had good linear relationships in the range of 0.01-0.2 mg/L, with all correlation coefficients greater than 0.99. The accuracy and precision of the method were verified using a standard recovery test with blank sesame-oil samples. Under the three standard levels of 0.04, 0.08, and 0.2 mg/kg, the recoveries of the five APs ranged from 71.3% to 97.8%, and the relative standard deviations (RSDs) ranged from 0.4% to 6.1%(n=6). The developed method is fast, accurate, sensitive, and has high throughput. Thus, it can realize the efficient screening, qualitative identification, and quantitative analysis of the 54 APs in sesame oil and provides a potential solution for the monitoring of other contaminants in food.

asb5a/asb5b Double Knockout Affects Zebrafish Cardiac Contractile Function.

Ankyrin repeat and suppression-of-cytokine-signaling box (Asb) proteins, a subset of ubiquitin ligase E3, include Asb5 with six ankyrin-repeat domains. Zebrafish harbor two asb5 gene isoforms, asb5a and asb5b. Currently, the effects of asb5 gene inactivation on zebrafish embryonic development and heart function are unknown. Using CRISPR/Cas9, we generated asb5a-knockout zebrafish, revealing no abnormal phenotypes at 48 h post-fertilization (hpf). In situ hybridization showed similar asb5a and asb5b expression patterns, indicating the functional redundancy of these isoforms. Morpholino interference was used to target asb5b in wild-type and asb5a-knockout zebrafish. Knocking down asb5b in the wild-type had no phenotypic impact, but simultaneous asb5b knockdown in asb5a-knockout homozygotes led to severe pericardial cavity enlargement and atrial dilation. RNA-seq and cluster analyses identified significantly enriched cardiac muscle contraction genes in the double-knockout at 48 hpf. Moreover, semi-automatic heartbeat analysis demonstrated significant changes in various heart function indicators. STRING database/Cytoscape analyses confirmed that 11 cardiac-contraction-related hub genes exhibited disrupted expression, with three modules containing these genes potentially regulating cardiac contractile function through calcium ion channels. This study reveals functional redundancy in asb5a and asb5b, with simultaneous knockout significantly impacting zebrafish early heart development and contraction, providing key insights into asb5's mechanism.

Corrigendum: Chunking in simultaneous interpreting: the impact of task complexity and translation directionality on lexical bundles.

[This corrects the article DOI: 10.3389/fpsyg.2023.1252238.].

Deep learning-based regional ECG diagnosis platform.

OBJECTIVE: To enable the intelligent diagnosis of a variety of common Electrocardiogram (ECG), we investigate the deep learning-based ECG diagnosis system. METHODS: From January 2015 to December 2019, four consecutive years of 100,120 conventional 12-lead ECG data were collected in our hospital. Utilizing this dataset, we constructed a deep learning model designed to intelligently diagnose prevalent ECG anomalies by employing a multi-task learning framework. The system performance was evaluated using various metrics, including sensitivity, specificity, negative predictive value, positive predictive value, and so forth. Additionally, we employed an ECG intelligent diagnostic platform for clinical application to undertake real-time online analysis of 2500 conventional 12-lead ECG samples in June 2020, aiming to validate our model. At this stage, we compared the performance of our model against the traditional manual identification method. RESULTS: The efficacy of the ECG intelligent diagnostic model was notably high for common and straightforward ECG patterns, such as sinus rhythm (F1 = 98.01%), sinus tachycardia (F1 = 96.26%), sinus bradycardia (F1 = 94.88%), and a normal electrocardiogram (F1 = 91.71%), as well as for Premature Ventricular Contractions (F1 = 91.62%). Nevertheless, when diagnosing rarer and more intricate ECG anomalies, the system requires an increased number of samples to refine the deep learning models. During the validation stage, our model exhibited better efficiency in terms of accuracy, labor time and labor cost when compared to the manual identification approach. CONCLUSIONS: Our deep learning-driven intelligent ECG diagnostic model clearly demonstrates significant clinical utility. The integrated artificial intelligence diagnosis system not only has the potential to augment physicians in their diagnostic processes but also offers a viable avenue to reduce associated labor costs.

Polydatin alleviates sepsis­induced acute lung injury via downregulation of Spi­B.

Sepsis-induced acute lung injury (ALI) is related to the dysregulation of inflammatory responses. Polydatin supplement was reported to exhibit anti-inflammatory effects in several diseases. The present study aimed to investigate the role of polydatin in sepsis-induced ALI. A cecum ligation and puncture (CLP)-induced mouse ALI model was established first and the pathological changes of lung tissues were assessed using hematoxylin and eosin staining. Meanwhile, to mimic sepsis-induced ALI in vitro, pulmonary microvascular endothelial cells (PMVECs) were treated with lipopolysaccharide (LPS). Pro-inflammatory cytokines levels were measured in lung tissues and PMVECs using ELISA. Reverse transcription-quantitative PCR was used to measure the mRNA levels of Spi-B in lung tissues and PMVECs. Moreover, the expression levels of Spi-B, p-PI3K, p-Akt, and p-NF-κB in lung tissues and PMVECs were determined using western blotting. The data revealed that polydatin attenuated CLP-induced lung injury and inhibited sepsis-induced inflammatory responses in mice. Furthermore, polydatin significantly inhibited the expression of Spi-B, p-PI3K, p-Akt, and p-NF-κB in lung tissues of mice subjected to CLP-induced ALI, while this phenomenon was reversed through Spi-B overexpression. Consistently, the anti-inflammatory effect of polydatin was abolished by Spi-B overexpression. Taken together, the current findings revealed that polydatin alleviated sepsis-induced ALI via the downregulation of Spi-B.

Utilizing grayscale ultrasound-based radiomics nomogram for preoperative identification of triple negative breast cancer.

PURPOSE: This study aimed to develop a radiomics nomogram based on grayscale ultrasound (US) to distinguish triple-negative breast cancer (TNBC) from non-triple-negative breast cancer (NTNBC) prior to surgery. METHODS: A retrospective analysis of 454 breast carcinoma patients confirmed by pathology was conducted, with 317 patients in the training dataset (59 with TNBC) and 137 patients in the validation dataset (27 with TNBC). Clinical information, conventional US features, and radiomics features were collected, and the Radscore model was constructed after feature selection. Independent risk factors were identified using univariate and multivariate logistic regression analysis. The nomogram model was assessed using the receiver operating characteristic (ROC) curve analysis, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: Tumor shape, margin, and calcification were independent risk factors in the clinical prediction model. Additionally, 16 radiomics features were selected to construct the Radscore model out of a total of 474 extracted features. The radiomics nomogram model, which incorporated tumor shape, margin, calcification, and Radscore, achieved an AUC value of 0.837 in the training dataset and 0.813 in the validation dataset, outperforming both the Radscore and clinical models in terms of predictive performance. The significant improvement of NRI and IDI indicated that the Radscore may be useful biomarkers for TNBC. CONCLUSION: The US-based radiomics nomogram showed satisfactory preoperative prediction of TNBC.