Lymph-derived chemokines direct early neutrophil infiltration in the lymph nodes upon Staphylococcus aureus skin infection.

A large number of neutrophils infiltrate the lymph node (LN) within 4 h after Staphylococcus aureus skin infection (4 h postinfection [hpi]) and prevent systemic S. aureus dissemination. It is not clear how infection in the skin can remotely and effectively recruit neutrophils to the LN. Here, we found that lymphatic vessel occlusion substantially reduced neutrophil recruitment to the LN. Lymphatic vessels effectively transported bacteria and proinflammatory chemokines (i.e., Chemokine [C-X-C motif] motif 1 [CXCL1] and CXCL2) to the LN. However, in the absence of lymph flow, S. aureus alone in the LN was insufficient to recruit neutrophils to the LN at 4 hpi. Instead, lymph flow facilitated the earliest neutrophil recruitment to the LN by delivering chemokines (i.e., CXCL1, CXCL2) from the site of infection. Lymphatic dysfunction is often found during inflammation. During oxazolone (OX)-induced skin inflammation, CXCL1/2 in the LN was reduced after infection. The interrupted LN conduits further disrupted the flow of lymph and impeded its communication with high endothelial venules (HEVs), resulting in impaired neutrophil migration. The impaired neutrophil interaction with bacteria contributed to persistent infection in the LN. Our studies showed that both the flow of lymph from lymphatic vessels to the LN and the distribution of lymph in the LN are critical to ensure optimal neutrophil migration and timely innate immune protection in S. aureus infection.

Trace element levels in the muscles of three tern species (Aves: Laridae) from the western Arabian Gulf: environmental assessment and implications for conservation.

In the Arabian Gulf (called also Persian Gulf; hereafter 'the Gulf'), Jana and Karan Islands are recognized as one of the most Important Bird Areas in the region. Many migratory breeding seabirds, like the Greater Crested Tern Thalasseus bergii, White-cheeked Tern Sterna repressa and Bridled Tern Onychoprion anaethetus, depend on these islands during the breeding season. However, these aquatic wildlife species are suffering from intensified urban and industrial coastal development and various contamination events including wars and related oil spills. In this study, we used these three piscivorous top predator birds to analyse the levels of 19 trace elements (TEs; i.e. Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, Pb, Sr, V and Zn) in 15 muscular tissue samples from Jana and Karan Islands. PERMANOVA analysis showed no difference in contamination profile between sites nor between species probably due to their spatial and ecological proximity and therefore similar levels of exposure to TEs. Comparing these levels with existing literature, our results showed no particular concern for all elements, except for Al (maximum values recorded = 116.5 µg g-1 d.w.) and, in two samples, Ba (33.67 µg g-1 d.w.) and Pb (5.6 µg g-1 d.w.). The results can be considered as an initial step for supplementary evaluations with a larger number of samples and specified time intervals for the collection of specimens. This study provided baseline information on the pollution status of these two ecologically important sites which require a continuous biomonitoring programme.

Hsa-miR-379 down-regulates Rac1/MLK3/JNK/AP-1/Collagen I cascade reaction by targeting connective tissue growth factor in human alveolar basal epithelial A549 cells.

OBJECTIVE: This study was aimed to screen and identify miRNAs that could regulate human CTGF gene and downstream cascade reaction Rac1/MLK3/JNK/AP-1/Collagen I by bioinformatics and experimental means. METHODS: TargetScan and Tarbase were used to predict miRNAs that may have regulatory effects on human CTGF gene. The dual-luciferase reporter gene assay was employed to verify the results obtained in bioinformatics. Human alveolar basal epithelial A549 cells were exposed to silica (SiO2) culture medium for 24 h to establish an in vitro model of pulmonary fibrosis, and bleomycin (BLM) of 100 ng/mL was used as a positive control. The miRNA and mRNA expression levels were determined by RT-qPCR, and the protein levels were measured by western blot in hsa-miR-379-3p overexpression group or not. RESULTS: A total of 9 differentially expressed miRNAs that might regulate the human CTGF gene were predicted. Hsa-miR-379-3p and hsa-miR-411-3p were selected for the subsequent experiments. The results of the dual-luciferase reporter assay showed that hsa-miR-379-3p could bind to CTGF, but hsa-miR-411-3p could not. Compared with the control group, SiO2 exposure (25 and 50 µg/mL) could significantly reduce the expression level of hsa-miR-379-3p in A549 cells. SiO2 exposure (50 µg/mL) could significantly increase the mRNA expression levels of CTGF, Collagen I, Rac1, MLK3, JNK, AP1, and VIM in A549 cells, while CDH1 level was significantly decreased. Compared with SiO2 + NC group, the mRNA expression levels of CTGF, Collagen I, Rac1, MLK3, JNK, AP1, and VIM were significantly decreased, and CDH1 level was significantly higher when hsa-miR-379-3p was overexpressed. At the same time, overexpression of hsa-miR-379-3p improved the protein levels of CTGF, Collagen I, c-Jun and phospho-c-Jun, JNK1 and phospho-JNK1 significantly compared with SiO2 + NC group. CONCLUSION: Hsa-miR-379-3p was demonstrated for the first time that could directly target and down-regulate human CTGF gene, and further affect the expression levels of key genes and proteins in Rac1/MLK3/JNK/AP-1/Collagen I cascade reaction.

Rapid Identification and Analysis of Ochratoxin-A in Food and Agricultural Soil Samples Using a Novel Semi-Automated In-Syringe Based Fast Mycotoxin Extraction (FaMEx) Technique Coupled with UHPLC-MS/MS.

In this work, a fast mycotoxin extraction (FaMEx) technique was developed for the rapid identification and quantification of carcinogenic ochratoxin-A (OTA) in food (coffee and tea) and agricultural soil samples using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection. The FaMEx technique advancement is based on two plastic syringes integrated setup for rapid extraction and its subsequent controlled clean-up process. In the extraction process, a 0.25-g sample and extraction solvent were added to the first syringe barrel for the vortex-based extraction. Then, the extraction syringe was connected to a clean-up syringe (pre-packed with C18, activated carbon, and MgSO4) with a syringe filter. Afterward, the whole set-up was placed in an automated programmable mechanical set-up for controlled elution. To enhance FaMEx technology performance, the various influencing sample pretreatment parameters were optimized. Furthermore, the developed FaMEx method indicated excellent linearity (0.9998 and 0.9996 for coffee/tea and soil) with highly sensitive detection (0.30 and 0.29 ng/mL for coffee/tea and soil) and quantification limits (1.0 and 0.96 for coffee/tea and soil), which is lower than the toxicity limit compliant with the European Union regulation for OTA (5 ng/g). The method showed acceptable relative recovery (84.48 to 100.59%) with <7.34% of relative standard deviation for evaluated real samples, and the matrix effects were calculated as <-13.77% for coffee/tea and -9.7 for soil samples. The obtained results revealed that the developed semi-automated FaMEx/UHPLC-MS/MS technique is easy, fast, low-cost, sensitive, and precise for mycotoxin detection in food and environmental samples.

[Using Creative Thinking Teaching to Improve Abdominal Drainage Tube Care Integrity Among Two-Year Post Graduate Nurses (PGNs)].

BACKGROUND & PROBLEMS: The abdominal drainage tube is an important device used in disease treatment and life maintenance. Drainage tube slippage leads to complications that increase both length of stay and costs of care. Four and seven cases of drainage tube slippage were reported, respectively, in 2018 and 2019 in our trauma wards. Among these, 9 cases were under the care of nurses in their post graduate year (PGY) training program. PURPOSE: To increase to 94% the abdominal drainage tube care-completeness rate of nurses in the PGY program. METHODS: Methods used included: establishing a standardized care module for abdominal drainage tube in the trauma wards, using the "drainage tube model" and multimedia teaching material in education to enhance skill proficiency, flexibly adjusting education schedules, using a creative-thinking teaching model in education, employing direct observation to evaluate PGY nurses' abdominal drainage tube skills; and establishing a drainage tube skill proficiency audit mechanism. RESULTS: After the intervention, the rate of care completeness for the abdominal drainage tube rose to 98.1%, participant awareness rose to 100%, and the rate of abdominal drainage tube slippage reduced to 0%. CONCLUSIONS: This project achieved good outcomes that may be expanded horizontally to other surgical wards. The use of the creative-thinking teaching model in training activities received good feedback from the nurse participants and will be incorporated into in-service education standards along with the computerized direct observation of procedural skills in the PGY e-learning passport to strengthen the completeness of learning processes.

Genetic diversity and life-history traits of bonefish Albula spp. from the Red Sea.

The management of bonefishes Albula spp. has been hindered by unresolved species distributions and a general lack of life-history information. This study provides the first genetic species identifications of Albula spp. from the northern Indian Ocean. The roundjaw bonefish Albula glossodonta was documented in the Red Sea, and the smallscale bonefish A. oligolepis was identified in the Gulf of Aden with no evidence supporting sympatry. Estimates of genetic differentiation indicate three closely related lineages of A. glossodonta in the Red Sea, Indian Ocean and Pacific Ocean (Red Sea-Pacific Ocean, Fst = 0.295; Red Sea-Seychelles, Fst = 0.193; Pacific Ocean-Seychelles, Fst = 0.141). In addition, the authors provide the first life-history information of Albula spp. in the Indian Ocean. Age-based growth models of A. glossodonta from the Red Sea demonstrated statistically significant differences compared to previously published data from the Pacific Ocean. Spawning activity during winter months was derived from gonado-somatic index values of A. glossodonta from the Red Sea and corresponded with spawning seasonality previously documented for the species in the Pacific Ocean. The results of this study aid in refining biogeographical uncertainties of Albula spp. and illustrate the importance of collecting regional growth information for subsequent management of A. glossodonta.

Strengths and weaknesses in the long-term sustainability of two sympatric seabreams (Argyrops spinifer and Rhabdosargus haffara, Sparidae).

Argyrops spinifer and Rhabdosargus haffara are two sympatric seabream species making important contributions to fisheries landings in the western Arabian/Persian Gulf. We identified the strengths and weaknesses in the long-term sustainability of A. spinifer and R. haffara stocks by integrating multiple sources of data, including fisheries catch and effort statistics, life history traits, scientific trawl surveys and historical length frequency distribution. Four strengths were identified in A. spinifer: wide distribution of juveniles, positive association to the network of de facto fishing exclusion areas created by hundreds of oil-gas facilities, early maturation and the existence of large and old individuals. A. spinifer suffers from two potential weaknesses: slow growth rate and higher exploitation pressure on the small-sized individuals. R. haffara, on the other hand, has a strength of having a short life span and a fast growth rate, characteristics that make it robust to unfavourable conditions. R. haffara suffers from two weaknesses: the lack of association to the oil and gas facilities, and the preference for nearshore shallow waters with stronger negative anthropogenic impacts. Identified strengths and weaknesses of these two sparids provided a preliminary assessment about their long-term sustainability, as well as a roadmap about how to develop different management strategies to meet specific objectives.

Elastin Shapes Small Molecule Distribution in Lymph Node Conduits.

The spatial and temporal Ag distribution determines the subsequent T cell and B cell activation at the distinct anatomical locations in the lymph node (LN). It is well known that LN conduits facilitate small Ag distribution in the LN, but the mechanism of how Ags travel along LN conduits remains poorly understood. In C57BL/6J mice, using FITC as a fluorescent tracer to study lymph distribution in the LN, we found that FITC preferentially colocalized with LN capsule-associated (LNC) conduits. Images generated using a transmission electron microscope showed that LNC conduits are composed of solid collagen fibers and are wrapped with fibroblastic cells. Superresolution images revealed that high-intensity FITC is typically colocalized with elastin fibers inside the LNC conduits. Whereas tetramethylrhodamine isothiocyanate appears to enter LNC conduits as effectively as FITC, fluorescently-labeled Alexa-555-conjugated OVA labels significantly fewer LNC conduits. Importantly, injection of Alexa-555-conjugated OVA with LPS substantially increases OVA distribution along elastin fibers in LNC conduits, indicating immune stimulation is required for effective OVA traveling along elastin in LN conduits. Finally, elastin fibers preferentially surround lymphatic vessels in the skin and likely guide fluid flow to the lymphatic vessels. Our studies demonstrate that fluid or small molecules are preferentially colocalized with elastin fibers. Although the exact mechanism of how elastin fibers regulate Ag trafficking remains to be explored, our results suggest that elastin can be a potentially new target to direct Ag distribution in the LN during vaccine design.

Perinodal Adipose Tissue Participates in Immune Protection through a Lymphatic Vessel-Independent Route.

Lymphatic vessels remove and transport excess interstitial fluid to lymph nodes (LNs) for fluid balance and immune protection. LNs are typically surrounded by perinodal adipose tissue (PAT). However, PAT is a blood vessel-rich but lymphatic-rare tissue; therefore, how excess fluid in PAT is removed remains unclear. Using C57BL/6 mice, fluorescent dye tracing and transmission electron microscopy results suggest that fluid in PAT can travel to the LN via collagen I+ channels (PAT-LN conduits), merge into a collagen-rich space between the PAT and LN capsule (PAT-LN sinus), and may enter the LN via the LN capsule-associated conduits. This newly identified route of fluid flow allows fluid to enter the draining LN even when the afferent lymphatic vessels are blocked, indicating that fluid trafficking in PAT-LN conduits is not dependent on functional lymphatic vessels. Similar to lymphatic vessels, PAT-LN conduits can deliver Ags to the LN for immune protection. Additionally, Staphylococcus aureus from intradermal or i.v. infection may use PAT-LN conduits to infect PAT and stimulate PAT immune protection. Our studies revealed a new route of material exchange between PAT and the LN. Ag accumulation and bacterial infection in PAT demonstrate that PAT not only provides energy and regulatory factors, but can also directly participate in immune protection, indicating a new immune function of PAT for host immunity.

Changes E3 ubiquitin protein ligase 1 gene mRNA expression correlated with IgA1 glycosylation in patients with IgA nephropathy.

BACKGROUND: Recent genomewide association study suggested that the top single-nucleotide polymorphism, rs978056, in HECW1 gene (which encodes HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1) associated with the levels of galactose-deficient IgA1 (Gd-IgA1) in IgA nephropathy (IgAN). However, HECW1 expression in IgAN has not yet been examined. METHODS: In the following study, we have enrolled 40 patients with IgAN and 40 healthy controls. The expression level of HECW1, as well as plasma levels of Gd-IgA1 and IgA1, were determined detected. RESULTS: IgAN patients presented with significantly elevated Gd-IgA1 and IgA1 levels compared with those of the healthy controls (p < .001 and p = .03, respectively). We further divided the patients into two groups according to the median level of HECW1 (0.58). We found the levels of Gd-IgA1 and IgA1 were significantly higher in low HECW1 level group compared with those in high HECW1 level group (p = .02 and p = .04, respectively). And HECW1 mRNA expression had a significant inverse correlation with Gd-IgA1 levels in IgAN patients (r= -0.34, p = .03). It seemed that the risk genotype (rs978056 GG) was associated with reduced HECW1 expression in 80 Han Chinese from Beijing, although the difference was not significant (p = .09). No significant association with clinical and pathological manifestations was observed between patients with high and low levels of HECW1. CONCLUSION: We reported for the first time that HECW1 mRNA levels were negatively correlated with Gd-IgA1 levels. Our study points to a new regulatory mechanism of IgAN that can explain the aberrant glycosylation of IgA1.

Life history traits and temporal trends of abundance of the orange-spotted trevally (Carangoides bajad) from Saudi waters of the Gulf.

In this study we lay the groundwork for sustainability-oriented fisheries management, by estimating parameters the life history of orange-spotted trevally Carangoides bajad as well as trends of abundance in coral-reef habitats. We observed a new record of maximum size of 720 mm fork length. Carangoides bajad is a moderately long-lived (14 years) and slow-growing (K = 0.085 year-1 ) carangid species, closer to a K-selection species, with higher vulnerability to fishing and lower rates of recovery when the population level is low. Growth and biological composition in terms of length and age categories do not differ between the sexes, but females become mature faster. Reproductively active months (May-August) overlapped with those from Emirati waters further south. The abundance index showed a pronounced drop during 1990-1993, possibly in connection with habitat deterioration during the Gulf War (1990-1991) oil spill. The index increased gradually from 1994 and has fluctuated close to the reference level of 1985 up to the present. Considering the findings of large-sized and old-age individuals and abundance index from coral reefs close to its level three decades back, the C. bajad stock in the western part of The Gulf appears to be in healthy exploitation status despite growing harvesting rates.

DNA barcoding of marine fishes from Saudi Arabian waters of the Gulf.

We used the cytochrome oxidase subunit I (coI) gene DNA to barcode 117 endemic Gulf and cosmopolitan Indo-West Pacific fish species belonging to 54 families and 13 orders. Novel DNA barcodes were provided for 18 fish species (Trachinocephalus sp., Nematalosa sp., Herklotsichthys lossei, Upeneus doriae, Trachurus indicus, Apogonichthyoides taeniatus, Verulux cypselurus, Favonigobius sp., Suezichthus gracilis, Sillago sp., Brachirus orientalis, Pegusa sp., Lepidotrigla bispinosa, Lepidotrigla sp., Grammoplites suppositus, Hippichthys sp., Paramonacanthus sp. and Triacanthus sp.). The species delimitation analysis, conducted with Poisson tree processes- Bayesian PTP (PTP-bPTP) and nucleotide-divergence-threshold (NDT) models), found 137 and 119 entities respectively. Overall, NDT method, neighbour-joining species tree and the prior taxonomic assessment provided similar results. Among the 54 families considered, only 10 (Ariommatidae, Ephippidae, Leiognathidae, Nemipteridae, Plotosidae, Pomacanthidae, Pomacentridae, Priacanthidae and Rachycentridae) showed the occurrence of molecular diagnostic pure characters. The DNA barcoding database developed during this study will help ichthyologists to identify and resolve the taxonomic ambiguities they may encounter with the fishes occurring in The Gulf and throughout the region.

Corticosteroid for IgA Nephropathy: Are They Really Therapeutic?

BACKGROUND: IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to end-stage kidney disease. The therapy with corticosteroid in IgAN is still a worldwide problem that is confusing the clinicians. METHODS: MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) that compared corticosteroids with placebo and any other non-immunosuppressive agents in treating IgAN. Twelve RCTs involving 1,057 patients were included. RESULTS: Overall, we found that steroids had statistically significant effects in preventing the decline in renal function (relative risk 0.42, 95% CI 0.25-0.71, p < 0.001) and reducing proteinuria (SMD: -0.58 g/day, 95% CI -0.80 to -0.36 g/day) in patients with IgAN. The association between glucocorticoid and risk of kidney outcome was not modified by steroids' type (prednisone or methylprednisone), dose (≤30 or > 30 mg/day), duration (≤8 or > 8 months), or serum creatinine (< 1.10 or ≥1.10 mg/dL). But steroids increased the risk of side effects such as gastrointestinal and endocrinium symptoms. CONCLUSION: This study provides the clear beneficial effects of the steroids therapy on the kidney function and proteinuria, although it should be used with caution.

miR-139-5p inhibits epithelial-mesenchymal transition, migration and invasion of hepatocellular carcinoma cells by targeting ZEB1 and ZEB2.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths worldwide. miRNAs have been suggested to have important roles in HCC development. The purpose of this study was to determine the role of miR-139-5p in regulation of epithelial-mesenchymal transition (EMT) and metastasis of HCC cells. Expression levels of miR-139-5p in 49 HCC specimens with adjacent tissues and five HCC cell lines were assessed by quantitative RT-PCR. We found that miR-139-5p was down-regulated in 89.7% of the HCC tissue samples and all of the HCC cell lines. In addition, luciferase reporter assays validated direct binding of miR-139-5p to the 3' untranslated region of zinc finger E-box binding homeobox 1 (ZEB1) and ZEB2. Ectopic expression of miR-139-5p suppressed and miR-139-in promoted EMT, migration, and invasion in Hep3B and SMMC7721 cells. Furthermore, over-expression of ZEB1 and ZEB2 ablated the inhibitory effects of miR-139-5p on migration and invasion in HCC cells. Our study indicates that miR-139-5p functions as a suppressor of HCC EMT and metastasis by targeting ZEB1 and ZEB2, and it may be a therapeutic target for metastatic HCC.

Construction of m7G RNA modification-related prognostic model and prediction of immune therapy response in hepatocellular carcinoma.

Background: RNA plays an important role in tumorigenesis. Changes in RNA may cause changes in the biological function. The N7-methylguanosine (m7G) methylation modification performs an integral function in tumor progression as the most widely existed RNA modification. Hepatocellular carcinoma (HCC) is among the greatest threats to human health worldwide. Low detection rates remain the main cause of advanced disease progression. Therefore, finding significant biomarkers for prognosis prediction and immune therapy response in HCC is valuable and urgently needed. Methods: RNA expression and clinical data were acquired from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Different subtypes screening was finished by consensus cluster. Different expression was performed by R software. The results were validated by western blot (WB) methods. Genes with HCC prognostic potential were identified utilizing least absolute shrinkage and selection operator (LASSO) analyses. A prognosis model was established with the help of the risk score that we calculated. Related genes screening and protein-protein interactions (PPI) network construction were performed using the GeneMANIA database. Functional annotation was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) databases. In addition, gene set enrichment analysis (GSEA) of key genes and immune infiltration status were both done by R software. Finally, the immune infiltration was performed by cibersort method and single sample GSEA (ssGSEA) method. The response of immune therapy was validated by Tumor Immune Dysfunction and Exclusion database (TIDE) and the immune therapy cohort in GEO database. Results: We found that two different subtypes related with m7G RNA modification and four genes associated with m7G RNA modification were differentially expressed in the TCGA-Liver Hepatocellular Carcinoma (TCGA-LIHC) database. Additionally, to examine the value of these four genes in the HCC patients' prognoses according to the LASSO, we selected three genes, including WDR4, AGO2, and NCBP2, as prognostic related genes. Premised on the expression of these three genes, a risk score model and nomogram were constructed to provide a prediction of the HCC patients' prognoses. We performed functional annotation and created a PPI network based on the three genes (WDR4, NCBP2, and AGO2). Using R software, we performed the GSEA and immune regulation analyses. Finally, we predicted the relationship between the gene expression and the response of immune therapy. Conclusions: Our study suggests that high expression of m7G RNA modification subtype is related with poor prognosis and immune response. WDR4, AGO2, and NCBP2 are key regulators of m7G RNA modification which can be clinically promising biomarkers that can be used to treat HCC. In addition, our risk score model was shown to have a strong link to OS in patients with HCC.

Environmentally relevant concentrations of benzophenones exposure disrupt intestinal homeostasis, impair the intestinal barrier, and induce inflammation in mice.

The aim of this study is to investigate the adverse effects of benzophenones (BPs) on the intestinal tract of mice and the potential mechanism. F1-generation ICR mice were exposed to BPs (benzophenone-1, benzophenone-2, and benzophenone-3) by breastfeeding from birth until weaning, and by drinking water after weaning until maturity. The offspring mice were executed on postnatal day 56, then their distal colons were sampled. AB-PAS staining, HE staining, immunofluorescence, Transmission Electron Microscope, immunohistochemistry, Western Blot and RT-qPCR were used to study the effects of BPs exposure on the colonic tissues of offspring mice. The results showed that colonic microvilli appeared significantly deficient in the high-dose group, and the expression of tight junction markers Zo-1 and Occludin was significantly down-regulated and the number of goblet cells and secretions were reduced in all dose groups, and the expression of secretory cell markers MUC2 and KI67 were decreased, as well as the expression of intestinal stem cell markers Lgr5 and Bmi1, suggesting that BPs exposure caused disruption of intestinal barrier and imbalance in the composition of the intestinal stem cell pool. Besides, the expression of cellular inflammatory factors such as macrophage marker F4/80 and tumor necrosis factor TNF-α was elevated in the colonic tissues of all dose groups, and the inflammatory infiltration was observed, which means the exposure of BPs caused inflammatory effects in the intestinal tract of F1-generation mice. In addition, the contents of Notch/Wnt signaling pathway-related genes, such as Dll-4, Notch1, Hes1, Ctnnb1and Sfrp2 were significantly decreased in each high-dose group (P < 0.05), suggesting that BPs may inhibit the regulation of Notch/Wnt signaling pathway. In conclusion, exposure to BPs was able to imbalance colonic homeostasis, disrupt the intestinal barrier, and trigger inflammation in the offspring mice, which might be realized through interfering with the Notch/Wnt signaling pathway.

A novel artificial intelligence model for measuring fetal intracranial markers during the first trimester based on two-dimensional ultrasound image.

OBJECTIVE: To establish reference ranges of fetal intracranial markers during the first trimester and develop the first novel artificial intelligence (AI) model to measure key markers automatically. METHODS: This retrospective study used two-dimensional (2D) ultrasound images from 4233 singleton normal fetuses scanned at 11+0-13+6 weeks of gestation at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to July 2022. We analyzed 10 key markers in three important planes of the fetal head. Based on these, reference ranges of 10 fetal intracranial markers were established and an AI model was developed for automated marker measurement. AI and manual measurements were compared to evaluate differences, correlations, consistency, and time consumption based on mean error, Pearson correlation analysis, intraclass correlation coefficients (ICCs), and average measurement time. RESULTS: The results of AI and manual methods had strong consistency and correlation (all ICC values >0.75, all r values >0.75, and all P values <0.001). The average absolute error of both only ranged from 0.124 to 0.178 mm. AI achieved a 100% detection rate for abnormal cases. Additionally, the average measurement time of AI was only 0.49 s, which was more than 65 times faster than the manual measurement method. CONCLUSION: The present study first established the normal standard reference ranges of fetal intracranial markers based on a large Chinese population data set. Furthermore, the proposed AI model demonstrated its capability to measure multiple fetal intracranial markers automatically, serving as a highly effective tool to streamline sonographer tasks and mitigate manual measurement errors, which can be generalized to first-trimester scanning.

Directional asymmetry in gonad length indicates moray eels (Teleostei, Anguilliformes, Muraenidae) are "right-gonadal".

Directional asymmetry indicates a unidirectional deviation from perfect bilateral symmetry, which was rarely examined in the inner organs of the teleost (Teleostei) compared to external traits. This study examines the directional asymmetry in the gonad length of 20 species of moray eels (Muraenidae) and two outgroup species with 2959 individuals. We tested three hypotheses: (1) moray eel species did not exhibit directional asymmetry in the gonad length; (2) the directional asymmetry pattern was the same for all selected species; (3) the directional asymmetry was not related to the major habitat types, depth and size classes, and taxonomic closeness of the species. Moray eels were generally "right-gonadal", the right gonad length being constantly and significantly longer than the left one in all studied Muraenidae species. The degree of asymmetry varied among species and was not significantly related to taxonomic closeness. The habitat types, depth, and size classes had intermingled effects on observed asymmetry without a clear correspondence. The directional asymmetry in the gonad length is a unique and widely occurring phenomenon in the Family Muraenidae, which was likely a by-product in the evolutionary history without significant disadvantage in survival.

Preliminary Study on the Effect and Molecular Mechanism of Tetrandrine in Alleviating Pulmonary Inflammation and Fibrosis Induced by Silicon Dioxide.

This study aims to explore the molecular mechanism of tetrandrine (Tet) in alleviating pulmonary inflammation and fibrosis induced by silica (SiO2) from the perspective of autophagy. C57BL/6J mice were selected as experimental animals, and SiO2 was exposed by intranasal instillation. Tet was intervened by oral gavage. The mice were euthanized on the 7th and 42nd day of SiO2 exposure, and lung tissues were collected for histopathological, molecular biological, immunological, and transmission electron microscopy analysis. The results showed that SiO2 exposure could lead to significant lung inflammation and fibrosis, while Tet could significantly reduce SiO2 exposure-induced lung inflammation and fibrosis. Molecular mechanism research indicated that, compared with SiO2 expose group, Tet intervention could significantly reduce the expression levels of inflammatory cytokines and fibrosis markers (TNF-α, IL-1ß, MCP-1, TGF-ß1, HYP, Col-I, and Fn), and regulate the expression of key molecules ATG7, microtubule-associated protein 1 light chain 3B (LC3B), and P62 in the autophagy pathway to improve the blocking of autophagic flux, promote the recovery of autophagic lysosomal system function, and inhibit apoptosis. In summary, Tet can alleviate silica-induced lung inflammation and fibrosis, which may be achieved by regulating the expression of key molecules in the autophagy process and associated apoptotic pathway.

Exploration of the Pathogenesis of Chronic Obstructive Pulmonary Disease Caused by Smoking-Based on Bioinformatics Analysis and In Vitro Experimental Evidence.

This study was aimed at investigating the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by smoking-based on bioinformatics analysis and in vitro experimental evidence. The GEO, GEO2R, TargetScan, miRDB, miRWalk, DAVID, and STRING databases were used for bioinformatics analysis. The mRNA expression and the protein levels were determined by real-time PCR and ELISA. After taking the intersection of the diversified results of the databases, four differentially expressed miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) were screened out. Subsequently, a total of 57 target genes of the selected miRNAs were obtained. The results of DAVID analysis showed that the selected miRNAs participated in COPD pathogenesis through long-term potentiation, the TGF-ß signaling pathway, the PI3K-Akt signaling pathway, etc. The results of STRING prediction showed that TP53, EP300, and MAPK1 were the key nodes of the PPI network. The results of the confirmatory experiment showed that, compared with the control group, the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated, while the expression of MYB was down-regulated and the protein levels of ZEB1, MAPK1, and EP300 were increased. Taken together, miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) and their regulated target genes and downstream protein molecules (ZEB1, EP300, and MAPK1) may be closely related to the pathological process of COPD.