Comparative impact of pristine and aged microplastics with triclosan on lipid metabolism in larval zebrafish: Unveiling the regulatory role of miR-217.

The prevalence of microplastics (MPs), especially aged particles, interacting with contaminants like triclosan (TCS), raises concerns about their toxicological effects on aquatic life. This study focused on the impact of aged polyamide (APA) MPs and TCS on zebrafish lipid metabolism. APA MPs, with rougher surfaces and lower hydrophobicity, exhibited reduced TCS adsorption than unaged polyamide (PA) MPs. Co-exposure to PA/APA MPs and TCS resulted in higher TCS accumulation in zebrafish larvae, notably more with PA than APA. Larvae exposed to PA + TCS exhibited greater oxidative stress, disrupted lipid metabolism, and altered insulin pathway genes than those exposed to TCS. However, these negative effects were lessened in the APA + TCS group. Through miRNA-seq and miR-217 microinjection, it was revealed that PA + TCS co-exposure upregulated miR-217, linked to lipid metabolic disorders in zebrafish. Moreover, molecular docking showed stable interactions formed between PA, TCS, and the insulin signaling protein Pik3r2. This study demonstrated that PA and TCS co-exposure significantly inhibited the insulin signaling in zebrafish, triggering lipid metabolism dysregulation mediated by miR-217 upregulation, while APA and TCS co-exposure alleviated these disruptions. This research underscored the ecological and toxicological risks of aged MPs and pollutants in aquatic environments, providing crucial insights into the wider implications of MPs pollution.

NKAIN1, as an oncogene, promotes the proliferation and metastasis of breast cancer, affecting its prognosis.

Na, K-ATPase interaction (NKAIN) is a transmembrane protein family, which can interact with Na, K-ATPase ß1 subunit. NKAIN1 plays an important role in alcohol-dependent diseases such as endometrial and prostate cancers. However, the relationship between NKAIN1 and human breast cancer has not been studied. Hence, this study aimed to explore the relationship between NKAIN1 expression and breast cancer. Data used in this study were mainly from the Cancer Genome Atlas, including differential expression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, multiple Cox regression analysis, co-expression gene analysis, and gene set enrichment analysis. Analyses were performed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunohistochemistry on 46 collected samples. The knockdown or overexpression of NKAIN1 in vitro in MCF-7 and MDA-MB-231 cell lines altered the proliferation and migration abilities of tumor cells. In vivo experiments further confirmed that NKAIN1 knockdown effectively inhibited the proliferation and migration of cancer cells. Therefore, our study identified NKAIN1 as an oncogene that is highly expressed in breast cancer tissues. The findings highlight the potential of NKAIN1 as a molecular biomarker of breast cancer.

Acute/chronic triclosan exposure induces downregulation of m6A-RNA methylation modification via mettl3 suppression and elicits developmental and immune toxicity to zebrafish.

Triclosan (TCS), a prevalent contaminant in aquatic ecosystems, has been identified as a potential threat to both aquatic biota and human health. Despite its widespread presence, research into the immunotoxic effects of TCS on aquatic organisms is limited, and the underlying mechanisms driving these effects remain largely unexplored. Herein, we investigated the developmental and immune toxicities of environmentally relevant concentrations of TCS in zebrafish, characterized by morphological anomalies, histopathological impairments, and fluctuations in cytological differentiation and biomarkers following both acute (from 6 to 72/120 hpf) and chronic exposure periods (from 30 to 100 dpf). Specifically, acute exposure to TCS resulted in a significant increase in innate immune cells, contrasted by a marked decrease in T cells. Furthermore, we observed that TCS exposure elicited oxidative stress and a reduction in global m6A levels, alongside abnormal expressions within the m6A modification enzyme system in zebrafish larvae. Molecular docking studies suggested that mettl3 might be a target molecule for TCS interaction. Intriguingly, the knock-down of mettl3 mirrored the effects of TCS exposure, adversely impacting the growth and development of zebrafish, as well as the differentiation of innate immune cells. These results provide insights into the molecular basis of TCS-induced immunotoxicity through m6A-RNA epigenetic modification and aid in assessing its ecological risks, informing strategies for disease prevention linked to environmental contaminants.

Comparative study of stretched-exponential and kurtosis models of diffusion-weighted imaging in renal assessment to distinguish patients with primary aldosteronism from healthy controls.

PURPOSE: To compare the ability of diffusion parameters obtained by stretched-exponential and kurtosis models of diffusion-weighted imaging (DWI) to distinguish between patients with primary aldosteronism (PA) and healthy controls (HCs) in renal assessment. MATERIALS AND METHODS: A total of 44 participants (22 patients and 22 HCs) underwent renal MRI with an 11 b-value DWI sequence and a 3 b-value diffusion kurtosis imaging (DKI) sequence from June 2021 to April 2022. Binary logistic regression was used to construct regression models combining different diffusion parameters. Receiver-operating characteristic (ROC) curve analysis and comparisons were used to evaluate the ability of single diffusion parameters and combined diffusion models to distinguish between the two groups. RESULTS: A total of six diffusion parameters (including the cortical anomalous exponent term [α_Cortex], medullary fractional anisotropy [FA_Medulla], cortical FA [FA_Cortex], cortical axial diffusivity [Da_Cortex], medullary mean diffusivity [MD_Medulla] and medullary radial diffusivity [Dr_Medulla]) were included, and 10 regression models were studied. The area under the curve (AUC) of Dr_Medulla was 0.855, comparable to that of FA_Cortex and FA_Medulla and significantly higher than that of α_Cortex, Da_Cortex and MD_Medulla. The AUC of the Model_all parameters was 0.967, comparable to that of Model_FA (0.946) and Model_DKI (0.966) and significantly higher than that of the other models. The sensitivity and specificity of Model_all parameters were 87.2% and 95%, respectively. CONCLUSION: The Model_all parameters, Model_FA and Model_DKI were valid for differentiating between PA patients and HCs with similar differentiation efficacy and were superior to single diffusion parameters and other models.

GREB1L overexpression is associated with good clinical outcomes in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor among women worldwide. GREB1L is a protein-coding gene. Previous studies have shown that GREB1L plays a vital role in lung and gastric adenocarcinoma. Currently, there is no relevant report about its role in breast cancer. METHODS: The Cancer Genome Atlas database was used to compare the expression level of GREB1L between tumor and normal tissues. The TISIDB website was used for prognosis analysis. The LinkedOmics database was used to predict the potential biological mechanism of GREB1L in breast cancer. Immunohistochemistry was used to detect the GREB1L expression level in breast tissue. Western blotting was used to detect the GREB1L expression level in cell lines. Transwell assays, CCK-8 cell proliferation assays, and colony formation assays were used to detect the migration, invasion, proliferation, and colony formation abilities of cells. Subcutaneous xenograft models were used to detect the in vivo tumor formation abilities of cells. RESULTS: GREB1L is highly expressed in breast cancer tissues and breast cancer cells. KEGG enrichment analysis suggested that GREB1L participates in the regulation of the Hedgehog signaling pathway; changes in GREB1L expression affected the migration and invasion abilities of MCF7 and MDA-MB-231 cells. Although changes in GREB1L expression did not affect their proliferation and colony formation abilities in vitro and in vivo, they affected the expression of tumor metastasis-related genes in vivo. The overexpression of GREB1L in breast cancer predicted a favorable prognosis. CONCLUSION: These results showed that GREB1L is involved in the development of breast cancer, and it may be a potential molecular marker for predicting the prognosis of breast cancer.

The Role of the Tumor Microenvironment in Triple-Positive Breast Cancer Progression and Therapeutic Resistance.

Breast cancer (BRCA) is a highly heterogeneous systemic disease. It is ranked first globally in the incidence of new cancer cases and has emerged as the primary cause of cancer-related death among females. Among the distinct subtypes of BRCA, triple-positive breast cancer (TPBC) has been associated with increased metastasis and invasiveness, exhibiting greater resistance to endocrine therapy involving trastuzumab. It is now understood that invasion, metastasis, and treatment resistance associated with BRCA progression are not exclusively due to breast tumor cells but are from the intricate interplay between BRCA and its tumor microenvironment (TME). Accordingly, understanding the pathogenesis and evolution of the TPBC microenvironment demands a comprehensive approach. Moreover, addressing BRCA treatment necessitates a holistic consideration of the TME, bearing significant implications for identifying novel targets for anticancer interventions. This review expounds on the relationship between critical cellular components and factors in the TPBC microenvironment and the inception, advancement, and therapeutic resistance of breast cancer to provide perspectives on the latest research on TPBC.

Azithromycin induces neurotoxicity in zebrafish by interfering with the VEGF/Notch signaling pathway.

Azithromycin (AZM) is a widely used antibiotic in both human and veterinary medicine, and its use has significantly increased during the COVID-19 pandemic. However, potential adverse effects of AZM on aquatic organisms have not been well studied. In this study, we explored the neurotoxicity of AZM in zebrafish and delved into its underlying mechanisms. Our results showed that AZM exposure resulted in a spectrum of detrimental effects in zebrafish, encompassing abnormal behaviors, damaged neuronal development, aberrant lateral line nervous system development, vascular malformations and perturbed expression of genes related to neural development. Moreover, we observed a concentration-dependent exacerbation of these neurotoxic manifestations with increasing AZM concentrations. Notably, AZM induced excessive cell apoptosis and oxidative stress damage. In addition, alterations in the expression levels of the genes involved in the VEGF/Notch signaling pathway were evident in AZM-exposed zebrafish. Consequently, we hypothesize that AZM may induce neurotoxicity by influencing the VEGF/Notch signaling pathway. To validate this hypothesis, we introduced a VEGF signaling inhibitor, axitinib, and a Notch signaling agonist, valproic acid, alongside AZM exposure. Remarkably, the administration of these rescue compounds significantly mitigated the neurotoxic effects induced by AZM. This dual verification provides compelling evidence that AZM indeed induces neurotoxicity during the early developmental stages of zebrafish, primarily through its interference with the VEGF/Notch pathway. Innovatively, our study reveals the molecular mechanism of AZM-induced neurotoxicity from the perspective of the close connection between blood vessels and nervous system. These findings provide new insights into the potential mechanisms underlying the neurotoxic effect of antibiotics and highlight the need for further investigation into the ecotoxicological effects of antibiotics on aquatic organisms and the potential risks to human health.

Combined analysis of the proteome and metabolome provides insight into microRNA-1174 function in Aedes aegypti mosquitoes.

BACKGROUND: Pathogenic viruses can be transmitted by female Aedes aegypti (Ae. aegypti) mosquitoes during blood-meal acquisition from vertebrates. Silencing of mosquito- and midgut-specific microRNA (miRNA) 1174 (miR-1174) impairs blood intake and increases mortality. Determining the identity of the proteins and metabolites that respond to miR-1174 depletion will increase our understanding of the molecular mechanisms of this miRNA in controlling blood-feeding and nutrient metabolism of mosquitoes. METHODS: Antisense oligonucleotides (antagomirs [Ant]) Ant-1174 and Ant-Ct were injected into female Ae. aegypti mosquitoes at 12-20 h posteclosion, and depletion of miR-1174 was confirmed by reverse transcription quantitative real-time PCR (RT-qPCR). Ant-1174-injected and control mosquitoes were collected before the blood meal at 72 h post-injection for tandem mass tag-based proteomic analysis and liquid chromatography-tandom mass spectrometry non-target metabolomic analysis to identify differentially expressed proteins and metabolites, respectively. RNA interference (RNAi) using double-stranded RNA (dsRNA) injection was applied to investigate the biological roles of these differentially expressed genes. The RNAi effect was verified by RT-qPCR and western blotting assays. Triglyceride content and ATP levels were measured using the appropriate assay kits, following the manufacturers' instructions. Statistical analyses were conducted with GraphPad7 software using the Student's t-test. RESULTS: Upon depletion of mosquito- and midgut-specific miR-1174, a total of 383 differentially expressed proteins (DEPs) were identified, among which 258 were upregulated and 125 were downregulated. Functional analysis of these DEPs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggested that miR-1174 plays important regulatory roles in amino acid metabolism, nucleotide metabolism, fatty acid metabolism and sugar metabolism pathways. A total of 292 differential metabolites were identified, of which 141 were upregulated and 151 were downregulated. Integrative analysis showed that the associated differential proteins and metabolites were mainly enriched in a variety of metabolic pathways, including glycolysis, citrate cycle, oxidative phosphorylation and amino acid metabolism. Specifically, the gene of one upregulated protein in miR-1174-depleted mosquitoes, purine nucleoside phosphorylase (PNP; AAEL002269), was associated with the purine, pyrimidine and niacin-nicotinamide metabolism pathways. PNP knockdown seriously inhibited blood digestion and ovary development and increased adult mortality. Mechanically, PNP depletion led to a significant downregulation of the vitellogenin gene (Vg); in addition, some important genes in the ecdysone signaling and insulin-like peptide signaling pathways related to ovary development were affected. CONCLUSIONS: This study demonstrates differential accumulation of proteins and metabolites in miR-1174-depleted Ae. aegypti mosquitoes using proteomic and metabolomic techniques. The results provide functional evidence for the role of the upregulated gene PNP in gut physiological activities. Our findings highlight key molecular changes in miR-1174-depleted Ae. aegypti mosquitoes and thus provide a basis and novel insights for increased understanding of the molecular mechanism involved in a lineage-specific miRNA in mosquito vectors.

[Clinical and genetic analysis of a patient with Craniofrontonasal syndrome].

OBJECTIVE: To explore the clinical feature and genetic etiology of a patient with Craniofacial nasal syndrome (CNFS). METHODS: A patient with CNFS who had presented at the Guiyang Maternal and Child Health Care Hospital on November 13, 2021 was selected as the study subject. Clinical data of the patient were collected. Peripheral venous blood samples were collected from the patient and her parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient, a 15-year-old female, had predominantly featured forehead bulging, hypertelorism, wide nasal dorsum and bifid nasal tip. Genetic testing revealed that she has harbored a heterozygous missense c.473T>C (p.M158T) variant of the EFNB1 gene, which was detected in either of her parents. By bioinformatic analysis, the variant has not been recorded in the HGMD and ClinVar databases, and no population frequency was recorded in the 1000 Genomes, ExAC, gnomAD and Shenzhou Genome Data Cloud databases. As predicted by the REVEL online software, the variant can confer deleterious effects on the gene or its product. Analysis using UGENE software showed the corresponding amino acid to be highly conserved among various species. Analysis with AlphaFold2 software suggested that the variant may affect the 3D structure and function of the Ephrin-B1 protein. Based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines and recommendation of Clinical Genome Resource (ClinGen), the variant was rated as pathogenic. CONCLUSION: Combining the patient's clinical features and genetic finding, the diagnosis of CNFS was confirmed. The heterozygous c.473T>C (p.M158T) missense variant of the EFNB1 gene probably underlay the disease in this patient. Above finding has provided a basis for the genetic counseling and prenatal diagnosis for her family.

Acute/chronic exposure to bisphenol A induced immunotoxicity in zebrafish and its potential association with pancreatic cancer risk.

Previous studies have confirmed that bisphenol A (BPA) induced immune toxicity and affected diseases, however, the underlying mechanism remains unknown. In the present study, zebrafish was employed as the model to assess the immunotoxicity and the potential disease risk of BPA exposure. Upon BPA exposure, a series of abnormalities were found, which included the increased oxidative stress, damaged innate and adaptive immune functions and the elevated insulin and blood glucose levels. According to the target prediction and RNA sequencing data of BPA, the differential expression genes were found enriched in immune- and pancreatic cancer-related pathway and process, and the potential role of stat3 in the regulation of these processes was revealed. The key immune- and pancreatic cancer-related genes were selected for further confirmation by RT-qPCR. Based on the changes in the expression levels of these genes, our hypothesis that BPA induced the occurrence of pancreatic cancer by modulating immune responses was further evidenced. Deeper mechanism was further disclosed by molecular dock simulation and survival analysis of key genes, proving that BPA stably bound to STAT3 and IL10 and STAT3 may serve as the target of BPA-inducing pancreatic cancer. These results are of great significance in deepening the molecular mechanism of immunotoxicity induced by BPA and our understanding of the risk assessment of contaminants.

Chlamydia psittaci Pneumonia Complicated with Lower Extremity Atherosclerotic Occlusive Disease.

Chlamydia is a zoonotic pathogen that mainly infects poultry and pet birds. This Gram-negative obligate intracellular parasite also causes human psittacosis, the severity of which varies from mild flu-like symptoms to life-threatening severe pneumonia, including sepsis, acute respiratory distress syndrome, and multiple organ failure. Inhalation of aerosols from contaminated bird excreta through the respiratory tract is the main route of transmission to humans. Here, we present a case of Chlamydia psittaci pneumonia accompanied by lower extremity atherosclerotic occlusive disease. A 48-year-old man was admitted to the emergency department with a four-day history of cough and dyspnea. A detailed history revealed his contact with domestic pigeons. The results of metagenomic next-generation sequencing of bronchoalveolar lavage fluid suggested C. psittaci infection. Antibacterial agents were switched to targeted doxycycline, but in the next week, skin examination revealed acrocyanosis of both lower extremities, and the remarkable palpable purpura progressively worsened. Re-examination of the lower extremity vascular ultrasound suggested left dorsalis pedis artery occlusion and right peroneal vein thrombosis, which resulted in the amputation of both legs. This case is the first report of C. psittaci pneumonia combined with arterioocclusive sclerosis of both lower extremities.

Physiological and transcriptome analysis of Dendrobium officinale under low nitrogen stress.

Nitrogen (N) is the main nutrient of plants, and low nitrogen usually affects plant growth and crop yield. The traditional Chinese herbal medicine Dendrobium officinale Kimura et. Migo is a typical low nitrogen-tolerant plant, and its mechanism in response to low nitrogen stress has not previously been reported. In this study, physiological measurements and RNA-Seq analysis were used to analyse the physiological changes and molecular responses of D. officinale under different nitrogen concentrations. The results showed that under low nitrogen levels, the growth, photosynthesis and superoxide dismutase activity were found to be significantly inhibited, while the activities of peroxidase and catalase, the content of polysaccharides and flavonoids significantly increased. Differentially expressed genes (DEGs) analysis showed that nitrogen and carbon metabolisms, transcriptional regulation, antioxidative stress, secondary metabolite synthesis and signal transduction all made a big difference in low nitrogen stress. Therefore, copious polysaccharide accumulation, efficient assimilation and recycling of nitrogen, as well as rich antioxidant components play critical roles. This study is helpful for understanding the response mechanism of D. officinale to low nitrogen levels, which might provide good guidance for practical production of high quality D. officinale .

Recent advances in hydrogels for preventing tumor recurrence.

Malignant tumors remain a high-risk disease with high mortality all over the world. Among all the cancer treatments, surgery is the primary approach in the clinical treatment of tumors. However, tumor invasion and metastasis pose challenges for complete tumor resection, accompanied by high recurrence rates and reduced quality of life. Hence, there is an urgent need to explore effective adjuvant therapies to prevent postoperative tumor recurrence and relieve the pain of the patients. Nowadays, the booming local drug delivery systems which can be applied as postoperative adjuvant therapies have aroused people's attention, along with the rapid development in the pharmaceutical and biological materials fields. Hydrogels are a kind of unique carrier with prominent biocompatibility among a variety of biomaterials. Due to their high similarity to human tissues, hydrogels which load drugs/growth factors can prevent rejection reactions and promote wound healing. In addition, hydrogels are able to cover the postoperative site and maintain sustained drug release for the prevention of tumor recurrence. In this review, we survey controlled drug delivery hydrogels such as implantable, injectable and sprayable formulations and summarize the properties required for hydrogels used as postoperative adjuvant therapies. The opportunities and challenges in the design and clinical application of these hydrogels are also elaborated.

Complete genome of Sphingomonas paucimobilis ZJSH1, an endophytic bacterium from Dendrobium officinale with stress resistance and growth promotion potential.

Sphingomonas paucimobilis ZJSH1 is an endophytic bacterium isolated from the roots of Dendrobium officinale with the ability to promote plant growth. It was found that the genome of strain ZJSH1 had gene fragment rearrangement compared with the genomes of the other four strains of S. paucimobilis, and the genome was integrated with phage genes. Functional analysis showed that the strain contained colonization-related genes, chemotaxis and invasion. A variety of genes encoding active materials, such as hormones (IAA, SA, ABA and zeaxanthin), phosphate cycle, antioxidant enzymes, and polysaccharides were identified which provide the strain with growth promotion and stress-resistant characteristics. Experiments proved that S. paucimobilis ZJSH1 grew well in media containing 80 g/L sodium chloride, 240 g/L polyethylene glycol and 800 µmol/L Cd2+, indicating its potential for resistance to stresses of salt, drought and cadmium, respectively. S. paucimobilis ZJSH1 is the only endophytic bacterium of this species that has been reported to promote plant growth. The analysis of its genome is conducive to understanding its growth-promoting mechanism and laying a foundation for the development and utilization of this species in the field of agriculture.

Comparative metabolism of THCA and THCV using UHPLC-Q-Exactive Orbitrap-MS.

Delta(9)-tetrahydrocannabinolic acid (THCA) and delta(9)-tetrahydrocannabivarin (THCV) are phytocannabinoids with a similar structure derived from Cannabis sativa and possess a variety of biological activities. However, the relationship between the metabolic characterisation and bioactivity of THCA and THCV remains elusive.To explore the relationship between the metabolism of THCA and THCV and their underlying mechanism of activity, human/mouse liver microsomes and mouse primary hepatocytes were used to compare the metabolic maps between THCA and THCV through comparative metabolomics. A total of 29 metabolites were identified containing 7 previously undescribed THCA metabolites and 10 previously undescribed THCV metabolites. Of these metabolites, THCA was transformed into an active metabolite of delta(9)-tetrahydrocannabinol (THC) in these three systems, while THCV was transformed into THC and CBD.Bioactivity assays indicated that all of these phytocannabinoids exhibited anti-inflammatory activity, but the effects of THCA and THCV were slightly different in macrophages RAW264.7. Prediction of ADMET lab demonstrated that THCV and its metabolites were endowed with the advantage of blood-brain barrier (BBB) penetration compared to THCA.In conclusion, this study highlighted that metabolism plays a critical role in the biological activity of phytocannabinoids.

Deep Learning-Based Acceleration of Compressed Sensing for Noncontrast-Enhanced Coronary Magnetic Resonance Angiography in Patients With Suspected Coronary Artery Disease.

BACKGROUND: The clinical application of coronary MR angiography (MRA) remains limited due to its long acquisition time and often unsatisfactory image quality. A compressed sensing artificial intelligence (CSAI) framework was recently introduced to overcome these limitations, but its feasibility in coronary MRA is unknown. PURPOSE: To evaluate the diagnostic performance of noncontrast-enhanced coronary MRA with CSAI in patients with suspected coronary artery disease (CAD). STUDY TYPE: Prospective observational study. POPULATION: A total of 64 consecutive patients (mean age ± standard deviation [SD]: 59 ± 10 years, 48.4% females) with suspected CAD. FIELD STRENGTH/SEQUENCE: A 3.0-T, balanced steady-state free precession sequence. ASSESSMENT: Three observers evaluated the image quality for 15 coronary segments of the right and left coronary arteries using a 5-point scoring system (1 = not visible; 5 = excellent). Image scores ≥3 were considered diagnostic. Furthermore, the detection of CAD with ≥50% stenosis was evaluated in comparison to reference standard coronary computed tomography angiography (CTA). Mean acquisition times for CSAI-based coronary MRA were measured. STATISTICAL TESTS: For each patient, vessel and segment, sensitivity, specificity, and diagnostic accuracy of CSAI-based coronary MRA for detecting CAD with ≥50% stenosis according to coronary CTA were calculated. Intraclass correlation coefficients (ICCs) were used to assess the interobserver agreement. RESULTS: The mean MR acquisition time ± SD was 8.1 ± 2.4 minutes. Twenty-five (39.1%) patients had CAD with ≥50% stenosis on coronary CTA and 29 (45.3%) patients on MRA. A total of 885 segments on the CTA images and 818/885 (92.4%) coronary MRA segments were diagnostic (image score ≥3). The sensitivity, specificity, and diagnostic accuracy were as follows: per patient (92.0%, 84.6%, and 87.5%), per vessel (82.9%, 93.4%, and 91.1%), and per segment (77.6%, 98.2%, and 96.6%), respectively. The ICCs for image quality and stenosis assessment were 0.76-0.99 and 0.66-1.00, respectively. DATA CONCLUSION: The image quality and diagnostic performance of coronary MRA with CSAI may show good results in comparison to coronary CTA in patients with suspected CAD. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: 2.

Facile construction of dibenzodioxo[3.3.1]nonanes bearing spirocyclohexadienones via domino [4 + 2] cycloaddition/C(sp3)-H oxidative dehydrogenation coupling reactions.

A novel palladium catalyzed homodimerization of ortho-hydroxyphenyl substituted p-QMs has been developed via [4 + 2] cycloaddition/oxidative dehydrogenation coupling domino reactions. An interesting palladium catalyzed intramolecular benzyl C-H oxidation dehydrogenation to form a transannular C(sp3)-O bond was found. This protocol provided an efficient method to construct various dibenzodioxo[3.3.1]nonanes bearing spirocyclohexadienones.

In situ Preparation of a Phospholipid Gel Co-Loaded with Methotrexate and Dexamethasone for Synergistic Rheumatoid Arthritis Treatment.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by arthrocele, cartilage damage and disability. Although several anti-RA drugs have been developed for long-term treatment, they require frequent local injection and lead to multiple adverse effects such as osteoporosis and myelosuppression. Purpose: Reducing the amount and frequency of anti-RA drugs methotrexate (MTX) and dexamethasone sodium phosphate (DSP) by local injection of phospholipid-based phase separation gel (PPSG) coloaded the two drugs, which presented PPSG-(+). Methods: First, We characterized PPSG-(+). And we used UV spectrophotometry and high performance liquid chromatography (HPLC) to detect drug concentration, which can clarify the drug release in vitro and in vivo, respectively. We also injected PPSG-(+) into the joint cavity of healthy rabbits to prove the safety of PPSG-(+). Then, we injected PPSG-(+) into the joint cavity of RA modeled rabbits to demonstrate the effect in anti-RA of PPSG-(+) including the thickness of joints, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß detection, hematoxylin-eosin (H&E) staining and computed tomography (CT) of joints. Results: Suspended particles show a tight and uniform arrangement in PPSG-(+). The gel underwent a phase transition at 20 min in vitro and 8 h in vivo, and vesicular structures reflecting its degradation and phase transition were observed in vivo. PPSG-(+) released both drugs in a sustained and fixed ratio for more than 14 days, while it proved to be safe for intra-articular injection and did not induce inflammation in a rabbit. Eventually, PPSG-(+) showed a good anti-RA effect and its potency can be maintained for 3 weeks. Conclusion: PPSG-(+) is a drug delivery system offering good biocompatibility and sustained release of MTX and DSP, leading to long-lasting anti-RA effect.

Local recurrence of mammary Paget's disease after nipple-sparing mastectomy and implant breast reconstruction: a case report and literature review.

OBJECTIVE: To provide a rare case of local recurrent Paget's disease after nipple-sparing mastectomy (NSM) with immediate breast reconstruction with 10 years of disease-free survival and to analyze the clinical and pathological characteristics. BACKGROUND: Mammary Paget's disease can be considered a rare type of local recurrence after breast cancer treatment, both in cases of conservative surgery and NSM with immediate breast reconstruction (Lohsiriwat et al, Ann Surg Oncol 19:1850-1855, 2012). Recurrent patients who present with nipple-areolar Paget's disease usually have unfavorable primary pathological characteristics and different latency periods. However, the recurrent status in patients with favorable primary pathological characteristics and the latency periods after NSM with immediate breast reconstruction are unclear. METHODS: First, we present a case of local recurrent Paget's disease in a young patient diagnosed with invasive breast carcinoma at age 30 who underwent NSM with primary silicone reconstruction. Then, the keywords "Paget's disease" and "nipple-sparing mastectomy" were selected. Articles including the local recurrence of Paget's disease after NSM were collected from the PubMed, Springer, and OVID databases, and the acquired relevant data were analyzed. We did not restrict our search by study design or publication date. RESULTS: Five studies describing 31 cases of local recurrent Paget's disease after NSM with implant breast reconstruction were included. The mean patient age reported was 45 years, and the average latency period from NSM to the local recurrence of Paget's disease was 40.2 months. Recurrent tumor histological features were Paget's disease with ductal carcinoma in situ (DCIS) in 16 patients (50%), Paget's disease without DCIS in 13 patients (40.6%), and Paget's disease with ductal intraepithelial neoplasia (DIN) in 3 patients (9.4%). The primary tumor histological feature was estrogen receptor (ER)(-)/progesterone receptor (PR)(-)/human epidermal growth factor receptor (HER-2)(+) in 21 patients (77.8%). Neither locoregional relapse nor metastatic events were found in these recurrent patients who accepted NAC excision after 4-5 years of follow-up. Our reported case showed that the patient experienced pregnancy and lactation after primary adjuvant chemotherapy and endocrine therapy. However, she developed an eczematoid lesion in the NAC 120 months after breast surgery. The histopathological examination was consistent with Paget's disease of the breast. Complete NAC and breast silicone prosthesis removal were performed. The patient accepted no systematic or local therapy and is currently alive. It is noteworthy that the biological features of the primary tumor were ER(+), PR(+), and HER-2(-); however, the recurrent tumor changed to ER(-), PR(-), and HER-2(+). CONCLUSIONS: The local recurrence of Paget's disease after NSM is uncommon; it may develop at a very early age and have a very long time to recurrence, as in our patient, who presented with recurrence 10 years after primary surgery. Surgeons should be wary of local recurrence of the nipple-areola complex after NSM in patients with ER-negative and HER-2-positive primary tumors. However, patients with ER/PR-positive and HER-2-negative tumors should not be neglected; we reported a case of an ER/PR-positive and HER-2-negative primary tumor, and ER-positive recurrent cases have the longest latency period. The local recurrence rate of Paget's disease after NSM is low, and the prognosis is good in recurrent patients who accept further extensive NAC excision. Further systematic treatment was not considered for this patient.

Paracandidimonas lactea sp. nov., a urea-utilizing bacterium isolated from landfill.

A urea-utilizing bacterium, designated Q2-2 T, was isolated from landfill. Cells of strain Q2-2 T were Gram stain-negative, aerobic, short-rod bacteria. Strain Q2-2 T was observed to grow at a temperature range of 15-37℃ (optimum 30 â„ƒ), a pH range of 5.5-9.5 (optimum pH 8.0) and 0-4% (w/v) NaCl (optimum 1%). The major respiratory quinone was Q-8, and the major polar lipids were diphosphatidyl glycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, and phosphatidyl glycerol. Based on the 16S rRNA gene sequence, strain Q2-2 T had the highest similarity with Paracandidimonas caeni 24 T (98.0%), followed by Pusillimonas soli MJ07T (97.5%), Parapusillimonas granuli Ch07T (97.2%), Pusillimonas ginsengisoli DCY25T (97.1%) and Paracandidimonas soli IMT-305 T (96.4%). The ANI values between strain Q2-2 T and the above related type strains were 71.02%, 73.52%, 74.32%, 74.59% and 72.29%, respectively. The DNA G + C content of strain Q2-2 T was 61.1%. Therefore, strain Q2-2 T represents a novel species of the genus Paracandidimonas, for which the name Paracandidimonas lactea sp. nov. (type strain Q2-2 T = CGMCC 1.19179 T = JCM 34906 T) is proposed.