Differences in resting-state brain activity in first-episode drug-naïve major depressive disorder patients with and without suicidal ideation.

Despite altered brain activities being associated with suicidal ideation (SI), the neural correlates of SI in major depressive disorder (MDD) have remained elusive. We enrolled 82 first-episode drug-naïve MDD patients including 41 with SI and 41 without SI, as well as 41 healthy controls (HCs). Resting-state functional and structural MRI data were collected. The measures of fractional amplitude of low-frequency fluctuation (fALFF) and grey matter volume (GMV) were calculated and compared. Compared with HCs, patients with SI exhibited increased fALFF values in the right rectus gyrus and left medial superior frontal gyrus, middle frontal gyrus and precuneus. Decreased GMV in the right parahippocampal gyrus, insula and middle occipital gyrus and increased GMV in the left superior frontal gyrus were detected in patients with SI. In addition, patients without SI demonstrated increased fALFF values in the right superior frontal gyrus and decreased fALFF values in the right postcentral gyrus. Decreased GMV in the left superior frontal gyrus, right medial superior frontal gyrus, opercular part of inferior frontal gyrus, postcentral gyrus, fusiform gyrus and increased left supplementary motor area, superior occipital gyrus, right anterior cingulate gyrus and superior temporal gyrus were revealed in patients with SI. Moreover, in comparison with patients without SI, increased fALFF values were identified in the left precuneus of patients with SI. However, no significant differences were found in GMV between patients with and without SI. These findings might be helpful for finding neuroimaging markers predicting individual suicide risk and detecting targeted brain regions for effective early interventions.

Generative artificial intelligence to produce high-fidelity blastocyst-stage embryo images.

STUDY QUESTION: Can generative artificial intelligence (AI) models produce high-fidelity images of human blastocysts? SUMMARY ANSWER: Generative AI models exhibit the capability to generate high-fidelity human blastocyst images, thereby providing substantial training datasets crucial for the development of robust AI models. WHAT IS KNOWN ALREADY: The integration of AI into IVF procedures holds the potential to enhance objectivity and automate embryo selection for transfer. However, the effectiveness of AI is limited by data scarcity and ethical concerns related to patient data privacy. Generative adversarial networks (GAN) have emerged as a promising approach to alleviate data limitations by generating synthetic data that closely approximate real images. STUDY DESIGN, SIZE, DURATION: Blastocyst images were included as training data from a public dataset of time-lapse microscopy (TLM) videos (n = 136). A style-based GAN was fine-tuned as the generative model. PARTICIPANTS/MATERIALS, SETTING, METHODS: We curated a total of 972 blastocyst images as training data, where frames were captured within the time window of 110-120 h post-insemination at 1-h intervals from TLM videos. We configured the style-based GAN model with data augmentation (AUG) and pretrained weights (Pretrained-T: with translation equivariance; Pretrained-R: with translation and rotation equivariance) to compare their optimization on image synthesis. We then applied quantitative metrics including Fréchet Inception Distance (FID) and Kernel Inception Distance (KID) to assess the quality and fidelity of the generated images. Subsequently, we evaluated qualitative performance by measuring the intelligence behavior of the model through the visual Turing test. To this end, 60 individuals with diverse backgrounds and expertise in clinical embryology and IVF evaluated the quality of synthetic embryo images. MAIN RESULTS AND THE ROLE OF CHANCE: During the training process, we observed consistent improvement of image quality that was measured by FID and KID scores. Pretrained and AUG + Pretrained initiated with remarkably lower FID and KID values compared to both Baseline and AUG + Baseline models. Following 5000 training iterations, the AUG + Pretrained-R model showed the highest performance of the evaluated five configurations with FID and KID scores of 15.2 and 0.004, respectively. Subsequently, we carried out the visual Turing test, such that IVF embryologists, IVF laboratory technicians, and non-experts evaluated the synthetic blastocyst-stage embryo images and obtained similar performance in specificity with marginal differences in accuracy and sensitivity. LIMITATIONS, REASONS FOR CAUTION: In this study, we primarily focused the training data on blastocyst images as IVF embryos are primarily assessed in blastocyst stage. However, generation of an array of images in different preimplantation stages offers further insights into the development of preimplantation embryos and IVF success. In addition, we resized training images to a resolution of 256 × 256 pixels to moderate the computational costs of training the style-based GAN models. Further research is needed to involve a more extensive and diverse dataset from the formation of the zygote to the blastocyst stage, e.g. video generation, and the use of improved image resolution to facilitate the development of comprehensive AI algorithms and to produce higher-quality images. WIDER IMPLICATIONS OF THE FINDINGS: Generative AI models hold promising potential in generating high-fidelity human blastocyst images, which allows the development of robust AI models as it can provide sufficient training datasets while safeguarding patient data privacy. Additionally, this may help to produce sufficient embryo imaging training data with different (rare) abnormal features, such as embryonic arrest, tripolar cell division to avoid class imbalances and reach to even datasets. Thus, generative models may offer a compelling opportunity to transform embryo selection procedures and substantially enhance IVF outcomes. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a Horizon 2020 innovation grant (ERIN, grant no. EU952516) and a Horizon Europe grant (NESTOR, grant no. 101120075) of the European Commission to A.S. and M.Z.E., the Estonian Research Council (grant no. PRG1076) to A.S., and the EVA (Erfelijkheid Voortplanting & Aanleg) specialty program (grant no. KP111513) of Maastricht University Medical Centre (MUMC+) to M.Z.E. TRIAL REGISTRATION NUMBER: Not applicable.

NaLuF4:RE3+ (Dy3+, Tb3+, Eu3+, Tm3+): controllable morphology, multicolor light.

A series of emission-tunable NaLuF4:RE3+ (RE = Dy, Tb, Eu, Tm) phosphors were firstly synthesized by a glycine assisted one-step hydrothermal process. The structure and morphology were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results revealed that the samples were Na5Lu9F32, LuF3 and NaLuF4 and the size and shape of the products could be tuned just by adjusting the pH values of the initial reaction solutions or by adjusting the RE3+/NaF ratio or RE3+/NaBF4 ratio. The morphologies for the products include irregular particles, irregular blocks, octahedral shapes, hexagons, or micron sized hexagonal prisms. Furthermore, the photoluminescence properties of NaLuF4:Dy3+,Tb3+, NaLuF4:Tb3+,Eu3+, NaLuF4:Dy3+,Eu3+ and NaLuF4:Tm3+,Dy3+ were investigated in detail. Additionally, when co-doping Dy3+ with Tb3+ or Eu3+ or co-doping Tb3+with Eu3+ or co-doping Tm3+ with Dy3+ ions in the single component, colorful emission can be obtained by giving abundant blue, green, yellow, orange, and especially white-light-emission. All these properties indicate that the developed phosphor may potentially be used as single-component multicolor-emitting phosphors.

Plum blossom low molecular weight polypeptide protects HaCaT cells against UVB-induced oxidative damage in vitro and underlying mechanism.

BACKGROUND: Increasing amounts of ultraviolet radiation occur as ozone depletion causes the earth's ozone layer to be destroyed, making antioxidant efficacy a research hotspot. Previous studies on plum blossom have mostly focused on Volatile Oils, Flavonoids, Phenylpropanoids, and other compounds, whereas few studies have focused on low molecular weight polypeptide (LMWP) of plum blossom. This research provides a reference for the deep processing and utilization of plum blossom. OBJECTIVES: (a) Plum blossom low molecular weight polypeptides protect HaCaT cells against UVB-induced oxidative damage in vitro and the underlying mechanism. (b) Improve the theoretical basis for the intense processing and utilization of plum blossom. METHODS: The safe concentration of LMWP and the survival rate of HaCaT cells were determined using the CCK-8 experiment. The fluorescence intensity of reactive oxygen species (ROS) was identified using the dichlorofluorescin diacetate (DCFH-DA) method; Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were measured in ruptured cells; Western blot analysis was used to examine the expression levels of three proteins: nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and benzoquinone oxidoreductase 1 (NQO-1). RESULTS: It was noted that a certain concentration of LMWP could promote cell proliferation. In oxidatively damaged HaCaT cells, SOD levels and survival rates were markedly reduced, but ROS and MDA levels were elevated. However, after treatment with LMWP, the survival rate of the cells and SOD levels were markedly increased, and the levels of ROS and MDA were markedly decreased. As shown by Western blotting, the model group exhibited lower levels of Nrf2, HO-1, and NQO-1 expression than the control group, whereas LMWP-treated cells had significantly higher levels of Nrf2, HO-1, and NQO-1 expression than their model-treated counterparts. CONCLUSIONS: LMMP can effectively protect HaCaT cells against oxidative damage in vitro induced by UVB, and the underlying mechanism is linked to the activation of the transcription factor Nrf2.

Evidence that oncostatin M synergizes with IL-4 signaling to induce TSLP expression in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Oncostatin M (OSM) may promote type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) by inducing thymic stromal lymphopoietin (TSLP). OBJECTIVE: We sought to study the impact of OSM on TSLP synthesis and release from nasal epithelial cells (NECs). METHODS: OSM receptors, IL-4 receptors (IL-4R), and TSLP were evaluated in mucosal tissue and primary NECs from patients with CRSwNP by quantitative PCR and immunofluorescence. Air-liquid interface-cultured NECs were stimulated with cytokines, including OSM, and quantitative PCR, ELISA, Western blot, and flow cytometry were used to assess the expression of OSM receptors, IL-4R, and TSLP. RESULTS: Increased levels of OSM receptor ß chain (OSMRß), IL-4Rα, and TSLP were observed in nasal polyp tissues and primary epithelial cells from nasal polyps of patients with CRSwNP compared with control tissues or cells from control subjects. The level of expression of OSMRß in tissue was correlated with levels of both IL-4Rα and TSLP. OSM stimulation of NECs increased the expression of OSMRß and IL-4Rα. Stimulation with IL-4 plus OSM augmented the production of TSLP; the response was suppressed by a signal transducer and activator of transcription 6 inhibitor. Stimulation of NECs with IL-4 plus OSM increased the expression of proprotein convertase subtilisin/kexin 3, an enzyme that truncates and activates TSLP. CONCLUSIONS: OSM increases the expression of IL-4Rα and synergizes with IL-4 to induce the synthesis and release of TSLP in NECs. Because the combination of IL-4 and OSM also augmented the expression of proprotein convertase subtilisin/kexin 3, these results suggest that OSM can induce both synthesis and posttranslational processing/activation of TSLP, promoting type 2 inflammation.

A novel online genomic counseling and variant interpretation certificate: Learning design, learning analytics, and evaluation.

In this paper we describe the analysis, planning, design, development, implementation and evaluation of a new online Graduate Certificate in Genomic Counselling and Variant Interpretation (GCGCVI) at The University of British Columbia (UBC). Genetic counselling is now a prerequisite for diagnostic genomic testing in many countries, demanding that genetic counselling practitioners have up-to-the-moment genomic counselling skills and knowledge. Current practitioners reported a desire for more training in this rapidly developing field: our international survey revealed substantial interest in online continuing education addressing themes such as testing and clinical bioinformatics, applied variant interpretation, evidence-based genomic counselling, and other emerging genomic topics. However, our market analysis found no post-graduate program globally that offered such training. To fill this gap, our oversight team of genetic counsellors and geneticists therefore guided development of curriculum and materials, and online learning specialists developed rigorous interactive asynchronous online graduate courses through collaboration with subject matter experts, following best practices in online learning design. Since launch in September 2020, we have gathered learner feedback using surveys and focus groups, and we have used learning analytics to understand how learners engaged with each other and with course materials. Together, these have helped us understand learner behaviour and guide the continuous process of design improvement to support the learning goals of this audience of professional learners. Our courses have been reviewed and approved by the UBC Faculty of Medicine, UBC Senate, and the Province of British Columbia Ministries of Advanced Education and Health, and assessed by the National Society of Genetic Counselors (NSGC, USA) and the Canadian Association of Genetic Counsellors (CAGC) to enable learners to receive North American continuing education credits. To date, 151 individuals from 18 countries have succeeded in one or more course and 43 have completed the entire certificate.

Analysis of Pediatric Surgical Disease Spectrum in a Tertiary Hospital.

Objective: To analyze the main disease composition of children hospitalized in pediatric surgery, explore the correlation between disease types and gender, and provide a reference for hospital management and pediatric disease prevention. Methods: Using ICD-10 codes as the classification standard for disease diagnosis, a statistical analysis was conducted on the disease composition of children hospitalized in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from January 1, 2015, to December 31, 2015, followed by the establishment of a clinical database. A total of 1647 male patients and 817 female patients were enrolled in the study, resulting in a male-to-female ratio of 2:1. The age range of the patients spanned from 0 to 18 years, with a marked imbalance in patient distribution among the various age groups. Statistical analysis was conducted using SPSS version 18.0 software. A chi-square test was performed to analyze the differences in the composition of disease systems and the composition of major diseases in terms of sex and age. Results: Pediatric patients were admitted with complex and diverse diseases in 2015, involving 15 systems of the human body and 400 diseases. Digestive system diseases, tumors, congenital malformations, and genitourinary system diseases were the top four diseases accounting for 83.5% of all pediatric cases. 561 patients were aged 0 years, accounting for 22.3% of all cases, while 1,801 patients fell within the 0-5 years age group, constituting 73.1% of the total. The differences in disease system composition among different sex and age groups of pediatric surgical inpatients were statistically significant (P = .001). There are statistically significant differences in the length of hospital stay and hospitalization costs among pediatric surgical inpatients in different age groups (P = .001). Conclusion: To strengthen the diagnosis and treatment of pediatric surgical diseases, we should strengthen the construction of key departments, optimize the consultation process according to the characteristics of children's disease spectrum, and improve the level of diagnosis and treatment of pediatric surgical diseases.

Studies on activation and regulation of the coagulation cascade in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP. OBJECTIVE: We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS. METHODS: Samples were collected from 135 subjects with CRSwNP, 80 subjects with chronic CRS without nasal polyps (NP), and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex, tissue factor (TF), and TF pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, immunohistochemistry, or immunofluorescence. Heteromeric complexes of TF with activated factor VII (FVII) and TF with activated FVII and FXa were assessed by coimmunoprecipitation and Western blotting. RESULTS: Increased levels of FXa, F1+2, and thrombin-antithrombin complex were detected in NP tissue compared to uncinate tissue from CRS and control subjects. Although free TF protein levels were not increased in NP, immunoprecipitation of TF in NP tissue revealed increased complexes of TF with FVII. Local expression of FVII was detected in sinonasal mucosa, and the ratio of TFPI to FXa was lower in NP tissue. CONCLUSION: The coagulation cascade is associated with NP compared to control and uncinate tissue from CRS patients, and TF and FVII are produced locally in sinonasal mucosa in patients. TF and FVII can activate the extrinsic coagulation pathway, suggesting that this pathway may activate fibrin deposition in CRSwNP. Reduced formation of the complex of FXa and TFPI in NP may reduce natural suppression of the extrinsic coagulation pathway in CRSwNP.

Global interpretation of novel alternative splicing events in human congenital pulmonary airway malformations: A pilot study.

Little is known about differentially expressed genes (DEGs) and alternative splicing (AS) landscapes in congenital lung malformations (CLMs). We applied reference-based assembly of sequencing reads from RNA sequencing (RNA-seq) libraries to identify DEGs and AS landscapes in the lesions and normal lung tissue from the most common types of CLMs, including congenital pulmonary airway malformation-Ⅰ (CPAM-Ⅰ), CPAM-Ⅱ, intralobar sequestration (ILS), and ILS with CPAM (ILS-CPAM). We analyzed the expression profiles and related biological functions of AS events (ASEs). We further constructed a co-expression regulatory network between RNA binding protein (RBP) genes and corresponding ASEs to explore the related pathways in the regulated network. Ten DEGs were identified in the four types of CLMs, including eight upregulated genes and two downregulated genes. Additionally, 16 differential ASEs were detected, including the genes MACF1, RFX2, and FBXL4. Gene ontology (GO) enrichment was mainly observed in embryonic visual malformation and apoptotic process, and the KEGG pathway mainly enriched in the PI3K/AKT signaling pathway. We also detected 13 differentially expressed RBPs among 1979 DEGs in CPAM-I, in which ASEs in the MACF1 gene and RBP genes TLR8 and PTRH1 were closely associated. Moreover, we confirmed that the expression levels of PTRH1, NSUN7, and DZIP1L abundantly increased and the expression levels of TLR8, MEF2A, and NIPBL decreased in the CPAM-I lung tissue compared with the controls. It is suggested that ASEs in different types of CLMs is prominently different from normal controls, and ASEs differences occurring in CPAM-I malformation tissue are dramatically different from other types, which demonstrates the complex pathogenesis of CLMs and provides foundations for future studies to elucidate the mechanisms of developing CLMs.

Progresses in processing technologies for special foods with ultra-long shelf life.

Foods for special applications have recently received much attention due to rapid development of space and military industries as well as to frequent occurrence of natural and man-made disasters. Since the way such foods are processed clearly and directly affects their consumer's acceptability and shelf life, it is of interest to explore in detail how these special foods can be processed. This article presents a review on the difficulties in the processing, application and storage as well as on how to ensure the shelf life and acceptability of special foods through the use of efficient processing technologies. Emphasis is made on the use of both conventional and alternative thermal processing and irradiation technologies. Appropriate packaging technologies for each of the discussed special foods are also mentioned along with the way to overcome the problem of product quality degradation. Through comparison and analysis, it is found that foods with different attributes require different technologies and processes to achieve desirable results. Combined use of multiple technologies has also noted to be advantageous.

Recent progress on quality improvement and detection technologies of special foods used for activities in space and aviation: a review.

This paper focuses on the development and evolution, quality improvement and research progress in the rapidly emerging area of new detection technologies of special foods for use in space and to some extent aviation. The quality improvement aspects covered in this review ranged from the special food processing technology, sterilization treatment and product packaging to new detection technologies for quality assurance based on DNA microarray technology, sensor, imaging technology, carbon nanotubes and novel probe technology.

Dizziness Result From Anomalous Origin of Left Common Carotid Artery.

BACKGROUND: The anomalous origin of the left common carotid artery from the pulmonary artery is extremely scarce. At present, there are few relevant research and medical treatment data. This case is intended to provide relevant information and share treatment experiences. Case information: A 6-year-old child was diagnosed with patent ductus arteriosus and underwent surgery five years ago with occasional dizziness. After examination, it was found that the abnormality of her left common carotid artery originated from the pulmonary artery, and the patient underwent arterial ligation with the monitoring of cerebral oxygen consumption by near-infrared spectroscopy after careful preoperative evaluation. At present, it has been two years after the operation, and the patient is in good condition and has received regular follow-up. CONCLUSION: For patients with an abnormal left common carotid artery from the pulmonary artery, after careful preoperative evaluation such as cerebral angiography, under the monitoring of cerebral oxygen consumption by near-infrared spectroscopy, ligation of the proximal end of the artery of abnormal origin is safe and feasible.

microRNA-320b suppresses HNF4G and IGF2BP2 expression to inhibit angiogenesis and tumor growth of lung cancer.

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.

Cancer-associated fibroblast-derived exosomal microRNA-24-3p enhances colon cancer cell resistance to MTX by down-regulating CDX2/HEPH axis.

MicroRNA-24-3p (miR-24-3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer-associated fibroblasts (CAFs) can secret exosomes to transfer miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF-derived exosomal miR-24-3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF-derived exosomal miR-24-3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR-24-3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR-24-3p was verified using ChIP and dual-luciferase reporter gene assays. Exosomes were isolated from miR-24-3p inhibitor-treated CAFs (CAFs-exo/miR-24-3p inhibitor), which were used in combination with gain-of-function and loss-of-function experiments and MTX treatment. CCK-8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR-24-3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR-24-3p and could up-regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down-regulated miR-24-3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR-24-3p was transferred into CC cells via CAF-derived exosomes. CAF-derived exosomal miR-24-3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF-derived exosomal miR-24-3p accelerated resistance of CC cells to MTX by down-regulating CDX2/HEPH axis.

Transcriptome analysis of lncRNA expression patterns in human congenital lung malformations.

OBJECTIVES: To explore the long non-coding RNA (lncRNA) expression pattern of congenital lung malformations on a genome-wide scale and investigate their potential biological function in four subtypes of congenital lung malformations. METHODS: We obtained both lesions and normal lung control tissues from the patients diagnosed with CPAM-I, CPAM-II, ILS, and ILS-CPAM, and underwent lobectomy (i.e., surgical removal of the whole lobe which contains the localized lesion as well as normal lung tissue). Then, we performed lncRNA transcriptome profiling in these tissues by RNA sequencing (RNA-seq). A comprehensive bioinformatics analysis was conducted to characterize the expression profiles and relevant biological functions and for multiple comparisons of lncRNA expression in the different subtypes of congenital lung malformation tissues. Furthermore, the lncRNA-mRNA co-expression network was constructed, and dysregulated mRNAs were functionally analyzed. Finally, gene set enrichment analysis (GSEA) was used to predict the potential molecular mechanism of the identified lncRNAs. RESULTS: A total of 5921 lncRNA transcripts were identified between congenital lung malformations tissues and normal lung control tissues. Compared with normal lung control, 481of these expressed lncRNAs were upregulated and 142 were downregulated in CPAM-I, 91 were upregulated and 14 were downregulated in CPAM-II, 39 were upregulated and 38 were downregulated in ILS, and 201 were upregulated and 38 were downregulated in ILS-CPAM. Unsupervised clustering and principal component analysis of the expressed lncRNAs visualized the differences between normal lung control and different subtypes of congenital lung malformations samples. We also confirmed significant differences in the composition of differentially expressed genes (DEGs) and the differentially expressed lncRNAs (DE lncRNAs) between CPAM-I and other subtypes of congenital lung malformations, as well as in normal lung control tissues, and observed enrichment of DEGs in the regulation of the immune system, cell projection organization, and inflammatory pathways. Finally, we identified the lncRNA FLJ26850 might be related to congenital lung malformations via ZNF473. CONCLUSIONS: Significant differences in lncRNAs expression patterns were observed between different subtypes of congenital lung malformations and normal control. The lncRNA FLJ26850 might be related to congenital lung malformations via ZNF473.

Hyperhomocysteinemia-induced Nrf2/HO-1 pathway suppression aggravates cardiac remodeling of hypertensive rats.

ABJECTIVE: Interaction of hypertension and hyperhomocysteinemia (HHcy) leads to enhanced cardiac remodeling in hypertensive heart disease. However, the mechanism of collagen accumulation and cardiac remodeling remains unclear. In this study, we attempted to evaluate the relationship between hypertension and HHcy in the context of cardiac remodeling and to explore its mechanism of action. METHODS: Wistar Kyoto (WKY) and spontaneous hypertension rats (SHR) were randomly divided into four groups, namely WKY group, WKY + HHcy group, SHR group and SHR + HHcy group. We measured blood pressure (BP), plasma homocysteine (Hcy), serum superoxide dismutase (SOD) and serum malondialdehyde (MDA). We also examined cardiac histopathology and gene and protein expression levels of Nrf2 and HO-1. RESULTS: Compared with the WKY group, myocardial interstitial and perivascular collagen deposition in the WKY + HHcy group, the SHR group and the SHR + HHcy group increased successively, indicating that cardiac remodeling gradually increased, and HHcy aggravated cardiac remodeling was more serious in hypertensive rats. SOD decreased gradually in the four groups, while MDA was on the contrary. WKY + HHcy and SHR + HHcy groups both suppressed Nrf2 and HO-1 expression and inhibited the translocation of Nrf2 from cytoplasm to nucleus compared with their control groups, and the SHR + HHcy group had a stronger inhibitory effect. CONCLUSION: HHcy enhanced cardiac remodeling in rats by enhancing oxidative stress, suppressing the Nrf2/HO-1 pathway and Nrf2 nuclear transport, and this inhibitory effect was stronger in the context of hypertension.

Cold-inducible RNA-binding protein contributes to tissue remodeling in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Cold-inducible RNA-binding protein (CIRP) is a newly identified damage-associated molecular pattern molecule. Its roles beyond promoting inflammation and in human diseases are poorly understood. This study aimed to investigate the involvement of CIRP in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Immunohistochemistry, quantitative RT-PCR, and ELISA were used to detect the expression of CIRP and matrix metalloproteinases (MMPs) in sinonasal mucosal samples and nasal secretions. Human nasal epithelial cells (HNECs) and THP-1 cells, a human monocytic/macrophage cell line, were cultured to explore the regulation of CIRP expression and MMP expression. RESULTS: Cytoplasmic CIRP expression in nasal epithelial cells and CD68+ macrophages in sinonasal tissues, and CIRP levels in nasal secretions were significantly increased in both patients with eosinophilic and noneosinophilic CRSwNP as compared to those in control subjects. IL-4, IL-13, IL-10, IL-17A, TNF-α, Dermatophagoides pteronyssinus group 1, and lipopolysaccharide induced the production and secretion of CIRP from HNECs and macrophages differentiated from THP-1 cells. CIRP promoted MMP2, MMP7, MMP9, MMP12, and vascular endothelial growth factor A (VEGF-A) production from HNECs, macrophages differentiated from THP-1 cells, and polyp tissues, which was inhibited by the blocking antibody for Toll-like receptor 4, but not advanced glycation end products. The expression of MMPs and VEGF-A in tissues correlated with CIRP levels in nasal secretions in patients with CRSwNP. CONCLUSIONS: The upregulated production and release of CIRP from nasal epithelial cells and macrophages may contribute to the edema formation in both eosinophilic and noneosinophilic CRSwNP by inducing MMP and VEGF-A production from epithelial cells and macrophages.

Acclimation of copper absorption ability of Candida utilis.

The use of inorganic copper in feed is hazardous. As probiotics of animals, Candida utilis can absorb copper ions and transform them to organic copper. This study aimed to domesticate the ability of C. utilis (CICC 32211) to absorb and transform copper ions. So, C. utilis (CICC 32211) was cultured in media with different concentrations of copper ions for 24, 48 and 72 h to identify the optimum copper ion concentration. C. utilis (CICC 32211) strains were domesticated for three generations, then the absorption and distribution of copper ions in the yeast cells were studied. We found that the optimum concentration of copper ions was 110 µg/mL. After 48 h, the number of yeast cells was low, but copper ion absorption efficiency was maximized (43.83%). Most of the enriched copper ions were distributed in the yeast cell wall (up to 30.58% when grown in the medium with 110 µg/mL copper ions), while the intracellular copper ion content was low (2.095%). High concentrations of copper ions affected the morphological structure, element content and distribution of yeast cells.

Hypoxic acclimation improves mitochondrial bioenergetic function in large yellow croaker Larimichthys crocea under Cu stress.

The purpose of this study was to investigate how pre-hypoxia exposure affected the mitochondrial structure and bioenergetic function of large yellow croaker in responding to Cu stress. Fish were acclimated to normoxia and 3.0 mg DO L-1 for 48 h, then subjected to 0 and 120 µg Cu L-1 for another 48 h. Hypoxic acclimation did not affect mitochondrial ultrastructure and reactive oxygen species (ROS), but reduced oxidative phosphorylation (OXPHOS) efficiency. Cu exposure impaired mitochondrial ultrastructure, increased ROS generation and inhibited OXPHOS efficiency. Compared with Cu exposure alone, hypoxic acclimation plus Cu exposure reduced ROS production and improved OXPHOS efficiency by enhancing mitochondrial respiratory control ratio, mitochondrial membrane potential, and activities and gene expressions of electron transport chain enzymes. In conclusion, hypoxic acclimation improved the mitochondrial energy metabolism of large yellow croaker under Cu stress, facilitating our understanding of the molecular mechanisms regarding adaptive responses of hypoxia-acclimated fish under Cu stress.

Low Dose of Folic Acid Can Ameliorate Hyperhomocysteinemia-Induced Cardiac Fibrosis and Diastolic Dysfunction in Spontaneously Hypertensive Rats.

To evaluate whether lowering plasma homocysteine (Hcy) levels at different doses of folic acid (FA) could reduce cardiac fibrosis and diastolic dysfunction in spontaneously hypertensive rats (SHRs) with hyperhomocysteinemia (Hhcy) and investigate the possible mechanism of action.We randomly divided 32 male SHRs into control, Hhcy, Hhcy + low-dose FA (LFA), and Hhcy + high-dose FA (HFA) groups. Echocardiography and Masson staining of cardiac tissue were used to assess diastolic function and cardiac fibrosis. Blood pressure (BP) and Hcy levels were measured during the experiment. We also measured the indicators of oxidative stress (OS) and examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes and proteins using real-time polymerase chain reaction (PCR), immunohistochemistry, and western blotting to explore the possible mechanism of action.FA treatment reversed SHR cardiomyocyte interstitial and perivascular collagen deposition and diastolic dysfunction exacerbated by Hhcy. These effects were associated with promoting the translocation of Nrf2 from the cytoplasm to the nucleus, activating HO-1 expression and inhibiting OS. However, HFA did not show any additional benefit from LFA in reducing cardiac injury.Even at a low dose, FA can ameliorate Hhcy-induced cardiac fibrosis and diastolic dysfunction in SHRs by activating Nrf2/HO-1 pathway and inhibiting OS, independent of BP, providing evidence for the efficacy of LFA in the treatment of hypertension associated with Hhcy.