Global miRNA dosage control of embryonic germ layer specification.

MicroRNAs (miRNAs) have essential functions during embryonic development, and their dysregulation causes cancer1,2. Altered global miRNA abundance is found in different tissues and tumours, which implies that precise control of miRNA dosage is important1,3,4, but the underlying mechanism(s) of this control remain unknown. The protein complex Microprocessor, which comprises one DROSHA and two DGCR8 proteins, is essential for miRNA biogenesis5-7. Here we identify a developmentally regulated miRNA dosage control mechanism that involves alternative transcription initiation (ATI) of DGCR8. ATI occurs downstream of a stem-loop in DGCR8 mRNA to bypass an autoregulatory feedback loop during mouse embryonic stem (mES) cell differentiation. Deletion of the stem-loop causes imbalanced DGCR8:DROSHA protein stoichiometry that drives irreversible Microprocessor aggregation, reduced primary miRNA processing, decreased mature miRNA abundance, and widespread de-repression of lipid metabolic mRNA targets. Although global miRNA dosage control is not essential for mES cells to exit from pluripotency, its dysregulation alters lipid metabolic pathways and interferes with embryonic development by disrupting germ layer specification in vitro and in vivo. This miRNA dosage control mechanism is conserved in humans. Our results identify a promoter switch that balances Microprocessor autoregulation and aggregation to precisely control global miRNA dosage and govern stem cell fate decisions during early embryonic development.

LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis.

BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe-/-PSMB8-AS1KI) and global Apoe and proteasome subunit-ß type-9 (Psmb9) double knockout mice (Apoe-/-Psmb9-/-). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe-/-PSMB8-AS1KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe-/- mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe-/-PSMB8-AS1KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-ß type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe-/- mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.

Genome-Wide Identification of Gene Loss Events Suggests Loss Relics as a Potential Source of Functional lncRNAs in Humans.

Gene loss is a prevalent source of genetic variation in genome evolution. Calling loss events effectively and efficiently is a critical step for systematically characterizing their functional and phylogenetic profiles genome wide. Here, we developed a novel pipeline integrating orthologous inference and genome alignment. Interestingly, we identified 33 gene loss events that give rise to evolutionarily novel long noncoding RNAs (lncRNAs) that show distinct expression features and could be associated with various functions related to growth, development, immunity, and reproduction, suggesting loss relics as a potential source of functional lncRNAs in humans. Our data also demonstrated that the rates of protein gene loss are variable among different lineages with distinct functional biases.

Quantitative model suggests both intrinsic and contextual features contribute to the transcript coding ability determination in cells.

Gene transcription and protein translation are two key steps of the 'central dogma.' It is still a major challenge to quantitatively deconvolute factors contributing to the coding ability of transcripts in mammals. Here, we propose ribosome calculator (RiboCalc) for quantitatively modeling the coding ability of RNAs in human genome. In addition to effectively predicting the experimentally confirmed coding abundance via sequence and transcription features with high accuracy, RiboCalc provides interpretable parameters with biological information. Large-scale analysis further revealed a number of transcripts with a variety of coding ability for distinct types of cells (i.e. context-dependent coding transcripts), suggesting that, contrary to conventional wisdom, a transcript's coding ability should be modeled as a continuous spectrum with a context-dependent nature.

Trophic Transfer of Halogenated Organic Pollutants in a Wetland Food Web: Insights from Compound-Specific Nitrogen Isotope of Amino Acids and Food Source Analysis.

A trophic position (TP) model (TPmix model) that simultaneously considered trophic discrimination factor and ßGlu/Phe variations was developed in this study and was first applied to investigate the trophic transfer of halogenated organic pollutants (HOPs) in wetland food webs. The TPmix model characterized the structure of the wetland food web more accurately and significantly improved the reliability of TMF compared to the TPbulk, TPAAs, and TPsimmr models, which were calculated based on the methods of stable nitrogen isotope analysis of bulk, traditional AAs-N-CSIA, and weighted ßGlu/Phe, respectively. Food source analysis revealed three interlocking food webs (kingfisher, crab, and frogs) in this wetland. The highest HOP biomagnification capacities (TMFmix) were found in the kingfisher food web (0.24-82.0), followed by the frog (0.08-34.0) and crab (0.56-11.7) food webs. The parabolic trends of TMFmix across combinations of log KOW in the frog food web were distinct from those of aquatic food webs (kingfisher and crab), which may be related to differences in food web composition and HOP bioaccumulation behaviors between aquatic and terrestrial organisms. This study provides a new tool to accurately study the trophic transfer of contaminants in wetlands and terrestrial food webs with diverse species and complex feeding relationships.

EPSTI1 promotes monocyte adhesion to endothelial cells in vitro via upregulating VCAM-1 and ICAM-1 expression.

Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.

Acute myocardial infarction with normal electrocardiogram and biomarkers of cardiac injury: A case report.

Patients with AMI usually present with the specific changes for electrocardiogram (ECG) and biomarkers of cardiac injury. Here, we present a rare case with chest pain and normal ECG and biomarkers of cardiac injury. Emergent coronary angiography revealed an occlusion of proximal left anterior descending coronary artery. The patient was diagnosed with AMI, and his symptom relieved after implantation of drug-eluting stents. Caution should be exercised for the exclusion of AMI in patients with chest pain and both normal ECG and biomarkers of cardiac injury.

IL-6 Mutation Attenuates Liver Injury Caused by Aeromonas hydrophila Infection by Reducing Oxidative Stress in Zebrafish.

Interleukin-6 (IL-6), a pleiotropic cytokine, plays a crucial role in acute stress induced by bacterial infection and is strongly associated with reactive oxygen species (ROS) production. However, the role of IL-6 in the liver of fish after Aeromonas hydrophila infection remains unclear. Therefore, this study constructed a zebrafish (Danio rerio) il-6 knockout line by CRISPR/Cas9 to investigate the function of IL-6 in the liver post bacterial infection. After infection with A. hydrophila, pathological observation showed that il-6-/- zebrafish exhibited milder liver damage than wild-type (WT) zebrafish. Moreover, liver transcriptome sequencing revealed that 2432 genes were significantly up-regulated and 1706 genes were significantly down-regulated in il-6-/- fish compared with WT fish after A. hydrophila infection. Further, gene ontology (GO) analysis showed that differentially expressed genes (DEGs) were significantly enriched in redox-related terms, including oxidoreductase activity, copper ion transport, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in pathways such as the PPAR signaling pathway, suggesting that il-6 mutation has a significant effect on redox processes in the liver after A. hydrophila infection. Additionally, il-6-/- zebrafish exhibited lower malondialdehyde (MDA) levels and higher superoxide dismutase (SOD) activities in the liver compared with WT zebrafish following A. hydrophila infection, indicating that IL-6 deficiency mitigates oxidative stress induced by A. hydrophila infection in the liver. These findings provide a basis for further studies on the role of IL-6 in regulating oxidative stress in response to bacterial infections.

Enhanced recovery after surgery care to reduce surgical site wound infection and postoperative complications for patients undergoing liver surgery.

This study comprehensively assessed the effect of enhanced recovery after surgery (ERAS) on wound infection and postoperative complications in patients undergoing liver surgery. The PubMed, EMBASE, MEDLINE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang electronic databases were searched to collect published studies on the use of ERAS in liver surgery until December 2022. Literature selection was performed independently by two investigators according to the inclusion and exclusion criteria, and quality evaluation and data extraction were performed. RevMan 5.4 software was used in this study. Compared with the control group, the ERAS group showed a significantly lower incidence of postoperative wound infection (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.41-0.84, P = .004) and overall postoperative complication rate (OR: 0.43, 95% CI: 0.33-0.57, P < .001) and significantly shorter postoperative hospital stay (mean difference: -2.30, 95% CI: -2.92 to -1.68, P < .001). Therefore, ERAS was safe and feasible when applied to liver resection, reducing the incidence of wound infection and total postoperative complications, and shortening the length of hospital stay. However, further studies are required to investigate the impact of ERAS protocols on clinical outcomes.

AnnoLnc2: the one-stop portal to systematically annotate novel lncRNAs for human and mouse.

With the abundant mammalian lncRNAs identified recently, a comprehensive annotation resource for these novel lncRNAs is an urgent need. Since its first release in November 2016, AnnoLnc has been the only online server for comprehensively annotating novel human lncRNAs on-the-fly. Here, with significant updates to multiple annotation modules, backend datasets and the code base, AnnoLnc2 continues the effort to provide the scientific community with a one-stop online portal for systematically annotating novel human and mouse lncRNAs with a comprehensive functional spectrum covering sequences, structure, expression, regulation, genetic association and evolution. In response to numerous requests from multiple users, a standalone package is also provided for large-scale offline analysis. We believe that updated AnnoLnc2 (http://annolnc.gao-lab.org/) will help both computational and bench biologists identify lncRNA functions and investigate underlying mechanisms.

Spatial Distribution, Bioconversion and Ecological Risk of PCBs and PBDEs in the Surface Sediment of Contaminated Urban Rivers: A Nationwide Study in China.

Surface sediments of polluted urban rivers can be a reservoir of hydrophobic persistent organic pollutants (POPs). In this study, we comprehensively assessed the contamination of two groups of POPs, that is, polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), in 173 black-odorous urban rivers in China. Spatial distribution of PCBs and PBDEs showed similar patterns but very different contamination levels in surface sediments, that is, average concentrations of 10.73 and 401.16 ng/g dw for the ∑PCBs and ∑PBDEs, respectively. Tetra-/di-CBs and deca-BDE are major PCBs and PBDEs and accounted for 59.11 and 95.11 wt % of the ∑PCBs and ∑PBDEs, respectively. Compared with the persistence of PBDEs, the EF changes of chiral PCBs together with previous cultivation evidence indicated indigenous bioconversion of PCBs in black-odorous urban rivers, particularly the involvement of uncharacterized Dehalococcoidia in PCB dechlorination. Major PCB sources (and their relative contributions) included pigment/painting (25.36%), e-waste (22.92%), metallurgical industry (13.25%), and e-waste/biological degradation process (10.95%). A risk assessment indicated that exposure of resident organisms in urban river sediments to deca-/penta-BDEs could pose a high ecological risk. This study provides the first insight into the contamination, conversion and ecological risk of PCBs and PBDEs in nationwide polluted urban rivers in China.

Adverse Events of Intense Pulsed Light Combined With Meibomian Gland Expression Versus Meibomian Gland Expression in the Treatment of Meibomian Gland Dysfunction.

BACKGROUND AND OBJECTIVE: To analyze the occurrence and causes of adverse events (AEs) in intense pulsed light (IPL) combined with meibomian gland expression (MGX) and MGX treatment alone for meibomian gland dysfunction (MGD). STUDY DESIGN/MATERIALS AND METHODS: A retrospective study was conducted on MGD patients treated in Wuhan Aier Hankou Eye Hospital from February 2018 to October 2019 to compare the AEs between IPL-MGX and MGX groups. Relevant AEs that occurred during the treatment and within 1 month after the patients' last treatment were recorded and the causes of the AEs were analyzed. RESULTS: A total of 2,282 patients received IPL-MGX and 1,407 received MGX treatment. No serious AEs occurred in both groups. There were 74 AEs in the IPL-MGX group, with an incidence of 3.24%, including 14 significant AEs (2 cases of epidemic keratoconjunctivitis, 1 recurrent herpes simplex keratitis (HSK), 9 new onsets of floaters, 1 recurrent glaucomatocyclitic crises, and 1 recurrent iridocyclitis). There were 27 AEs in the MGX group with a rate of 1.92%, including 4 significant AEs (2 cases of keratoconjunctivitis epidemic, 2 new cases of floaters). Compared with the IPL-MGX group, the incidence of AEs in the MGX group was lower (P = 0.017). CONCLUSIONS: Both IPL-MGX and MGX treatment are safe therapies with low risk for AEs. IPL treatment is not recommended for young children (age 10 or less) as well as patients with anterior uveitis or glaucomatocyclitic crises. The previous history of HSK and eyes with high myopia are advised to exercise caution in IPL treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Stratified aspartate aminotransferase-to-platelet ratio index accurately predicts survival in hepatocellular carcinoma patients undergoing curative liver resection.

The aspartate aminotransferase-to-platelet ratio index has been reported to predict prognosis of patients with hepatocellular carcinoma. This study examined the prognostic potential of stratified aspartate aminotransferase-to-platelet ratio index for hepatocellular carcinoma patients undergoing curative liver resection. A total of 661 hepatocellular carcinoma patients were retrieved and the associations between aspartate aminotransferase-to-platelet ratio index and clinicopathological variables and survivals (overall survival and disease-free survival) were analyzed. Higher aspartate aminotransferase-to-platelet ratio index quartiles were significantly associated with poorer overall survival (p = 0.002) and disease-free survival (p = 0.001). Multivariate analysis showed aspartate aminotransferase-to-platelet ratio index to be an independent risk factor for overall survival (p = 0.018) and disease-free survival (p = 0.01). Patients in the highest aspartate aminotransferase-to-platelet ratio index quartile were at 44% greater risk of death than patients in the first quartile (hazard ratio = 1.445, 95% confidence interval = 1.081 - 1.931, p = 0.013), as well as 49% greater risk of recurrence (hazard ratio = 1.49, 95% confidence interval = 1.112-1.998, p = 0.008). Subgroup analysis also showed aspartate aminotransferase-to-platelet ratio index to be an independent predictor of poor overall survival and disease-free survival in patients positive for hepatitis B surface antigen or with cirrhosis (both p < 0.05). Similar results were obtained when aspartate aminotransferase-to-platelet ratio index was analyzed as a dichotomous variable with cutoff values of 0.25 and 0.62. Elevated preoperative aspartate aminotransferase-to-platelet ratio index may be independently associated with poor overall survival and disease-free survival in hepatocellular carcinoma patients following curative resection.

Treatment of mixed and refractory post-tuberculosis tracheobronchial stenosis with L-shaped silicone stents: case series and a literature review.

The two patients included in the study had mixed and refractory post-tuberculosis tracheobronchial stenosis (PTTS), having experienced unsuccessful interventional therapies such as balloon dilation and V-shaped stent placement before the operation. Following the secure placement of L-shaped silicone stents, examinations with a fiberbronchoscope during the first and third months post-operation revealed a significant reduction in bronchial mucosa inflammation for both patients. Additionally, the opening diameter of the upper and lower branch segments increased, and chest CT scans indicated a noticeable absorption of left pulmonary lesions. Three months post-operation, fiberbronchoscopy confirmed the stable fixation of the stent without any movement. The patients exhibited substantial improvements in pulmonary function, dyspnea index, and blood gas analysis, with no reported adverse complications. After 7 months, a follow-up fiberbronchoscope for one case revealed excellent stent fixation. Simultaneously, the chest CT scan indicated favorable re-expansion. The placement of L-shaped silicone stents proves effective in preventing displacement, alleviating airway stenosis or obstruction, and ensuring the safety and efficacy of PTTS treatment - particularly in cases where V-shaped silicone stent placement has failed. To our knowledge, this is the first study describing the L-shaped silicone stent in two patients with PTTS.

Successful treatment of severe airway narrowing due to tuberculosis using special L-shaped silicone stentsThis article tells the story of two patients who suffered from a complex lung condition called post-tuberculosis tracheobronchial stenosis (PTTS). Imagine your airways - the tubes that carry air to your lungs - getting severely scarred and narrowed due to a past bout with tuberculosis. These two patients had tried previous treatments like balloon dilation (where a small balloon is inflated inside the narrowed airway to widen it) and using V-shaped stents (flexible supports placed in the airway to keep it open), but these methods didn't provide lasting relief. In this innovative approach, doctors used L-shaped silicone stents specifically designed to fit in the affected parts of the patients' airways. After placing these stents, regular checks showed remarkable improvements. The swelling in the airway lining reduced significantly, and the openings leading to the upper and lower parts of the lungs got wider. Chest X-rays (CT scans) even showed that the patient's left lung was healing well. Three months later, the stents stayed firmly in place, and neither patient experienced any problems. Breathing became easier, lung function tests improved, and blood tests showed better oxygen levels. Seven months down the line, one patient continued to do extremely well, with the stent securely fixed and the chest scan showing good lung expansion. This groundbreaking study shows that using L-shaped silicone stents can effectively treat PTTS when other methods fail. Not only do they stay in place, preventing blockages, but they also safely and effectively alleviate narrowing of the airways. It's the first time such L-shaped stents have been used successfully in PTTS patients, offering new hope for those facing similar challenges.

A comprehensive assessment of external exposure to persistent halogenated organic pollutants for residents in an e-waste recycling site, South China.

Human skin wipes from 30 participants, air, dust, and food items were collected from a former electronic waste site in South China to provide a comprehensive understanding of residents' exposure to halogenated flame retardants (HFRs) and polychlorinated biphenyls (PCBs). The total concentration of halogenated organic pollutants (HOPs) in the dust, air, food and skin wipes ranged 240-25000 ng/g, 130-2500 pg/m3, 0.08-590 ng/g wet weight, and 69-28000 ng/m2, respectively. Wild fish, vegetables, and air were dominated by PCBs, whereas dust, livestock, and poultry were dominated by HFRs. The HOP concentrations were several orders of magnitude higher in local foodstuffs than in market foodstuffs. The chemical composition on the forehead was remarkably different from that on the hand. The importance of different exposure routes depends on the residents' food choices, except decabromodiphenyl ethane (DBDPE). For residents who consumed a 100-foot diet (mainly egg) and local wild fish, diet ingestion overwhelmed other exposure routes, and PCBs were mainly contributed by fish and HFRs by egg. For residents who consumed market food, the dermal absorption of most PCB congeners and dust ingestion of highly brominated flame retardants were relatively prominent. Inhalation was found to be a crucial route for pentabromoethylbenzene (PBEB).

Tissue-Specific Distribution and Maternal Transfer of Persistent Organic Halogenated Pollutants in Frogs.

Persistent organic pollutants pose a great threat to amphibian populations, but information on the bioaccumulation of contaminants in amphibians remains scarce. To examine the tissue distribution and maternal transfer of organic halogenated pollutants (OHPs) in frogs, seven types of tissues from black-spotted frog (muscle, liver, kidney, stomach, intestine, heart, and egg) were collected from an e-waste-polluted area in South China. Among the seven frog tissues, median total OHP concentrations of 2.3 to 9.7 µg/g lipid weight were found (in 31 polychlorinated biphenyl [PCB] individuals and 15 polybrominated diphenyl ether [PBDE], dechlorane plus [syn-DP and anti-DP], bexabromobenzene [HBB], polybrominated biphenyl] PBB153 and -209], and decabromodiphenyl ethane [DBDPE] individuals). Sex-specific differences in contaminant concentration and compound compositions were observed among the frog tissues, and eggs had a significantly higher contaminant burden on the whole body of female frogs. In addition, a significant sex difference in the concentration ratios of other tissues to the liver was observed in most tissues except for muscle. These results suggest that egg production may involve the mobilization of other maternal tissues besides muscle, which resulted in the sex-specific distribution. Different parental tissues had similar maternal transfer mechanisms; factors other than lipophilicity (e.g., molecular size and proteinophilic characteristics) could influence the maternal transfer of OHPs in frogs. Environ Toxicol Chem 2024;43:1557-1568. © 2024 SETAC.

Implementation and effectiveness of a nurse navigation programme based on noddings' care theory in first-year undergraduate nursing students for professional identity and career planning: A quasi-experimental study.

AIMS: Development and evaluation of the effectiveness of a Nurse Navigation programme based on Noddings' Care theory on two dependent variables which were professional identity and career planning among first-year undergraduate nursing students. BACKGROUND: First-year undergraduate nursing students generally have a low sense of professional identity and career planning, resulting in a loss of nursing power after graduation. Implemention of a Nurse Navigation program based on Noddings' Care theory may be potentially useful in cultivating their professional identity and career planning. DESIGN: A quasi-experimental study. METHODS: A convenience sample of 122 first-year undergraduate nursing students from two medical universities was recruited between September 2021 and June 2022. Students in the experimental group (n = 63) participated in the Nurse Navigation programme based on Noddings' Care theory, which contained four core components, spreading over 50 lessons. Those in the control group (n = 59) underwent a traditional training programme with five components across 44 lessons. The two groups were compared in terms of their level of professional identity by Professional identity questionnaire for nurse students (PIQNS) and career planning by Career planning questionnaire (CPQ) after the training using the t-test. RESULTS: The mean score of professional identity in the experimental group increased significantly from 51.02 ± 8.46 at baseline to 58.02 ± 8.81 after the intervention (p < 0.001), with a large effect size (Cohen's d=0.810). Also, this post-intervention score was statistically significantly higher than that (52.86 ± 9.27) in the control group (p = 0.002), with a medium effect size (Cohen's d=0.571). The mean score of career planning in the experimental group increased significantly from 81.76 ± 9.86 at baseline to 94.52 ± 10.81 after the intervention (p < 0.001), with a large effect size (Cohen's d = 1.233). Also, this post-intervention score was statistically significantly higher than that (88.25 ± 9.30) in the control group (p < 0.001), with a medium effect size (Cohen's d=0.623). CONCLUSIONS: The Nurse Navigation programme based on Noddings' Care theory showed effectiveness in enhancing professional identity and career planning among first-year undergraduate nursing students in China. Further rigorous studies are needed to examine its effectiveness and long-term impacts on these students.

Occurrence, spatial distribution, and risk assessment of short- and medium-chain chlorinated paraffins in sediment from black-odorous rivers across China.

Chlorinated paraffins (CPs) were massively produced for varied industrial purposes, of which improper handling and consequent environmental release resulted in worldwide contamination. The present study investigated the occurrence and spatial distribution of short- and medium-chain chlorinated paraffins (SCCP/MCCPs) in 171 sediment samples from black-odorous urban rivers across China. Total SCCP and MCCP concentrations ranged from 8.3 to 9.4 × 104 (median: 1.1 × 103) ng/g dw, and from not-detected-value to 1.0 × 106 (median: 1.3 × 104) ng/g dw, respectively. No clear spatial distribution of SCCPs and MCCPs was observed since black-odorous urban rivers were polluted by point-sources of the SCCP/MCCPs. Significant positive correlations were identified between SCCP/MCCPs and total organic carbon, and between SCCP/MCCPs and other persistent organic matter, including polybrominated diethyl ethers, polychlorinated biphenyls, antibiotics, and plasticizers. The average ratios of MCCPs to SCCPs in most samples were divided into 11 and 16, implying the manufacturing and use of at least two types of CP technical mixtures in China. The composition of SCCP/MCCPs were similar to that in their commercial products. Ecological risk assessments by two approaches, including the Federal Environmental Quality Guidelines and Risk Quotient, both revealed that SCCP/MCCP in surface sediments confer an ecological risk. ENVIRONMENTAL IMPLICATION: SCCPs and MCCPs can be considered "hazardous materials" because of their massive production and their potential persistence, long-distance transfer, bioaccumulation potential, and toxicity. This research conducted a comprehensive study on SCCP/MCCP in black-odorous urban river sediments across China and revealed their environmental risk, which may improve understanding of SCCP/MCCP contamination characteristics.

A novel role for YPEL2 in mediating endothelial cellular senescence via the p53/p21 pathway.

Yippee-like 2 (YPEL2) is expressed in tissues and organs enriched in vascular networks, such as heart, kidney, and lung. However, the roles of YPEL2 in endothelial cell senescence and the expression of YPEL2 in atherosclerotic plaques have not yet been investigated. Here, we report the essential role of YPEL2 in promoting senescence in human umbilical vein endothelial cells (HUVECs) and the upregulation of YPEL2 in human atherosclerotic plaques. YPEL2 was significantly upregulated in both H2O2-induced senescent HUVECs and the arteries of aged mice. Endothelial YPEL2 deficiency significantly decreased H2O2-increased senescence-associated beta-galactosidase (SA-ß-gal) activity and reversed H2O2-inhibited cell viability. Additionally, endothelial YPEL2 knockdown reduced H2O2-promoted THP-1 cell adhesion to HUVECs and downregulated ICAM1 and VCAM1 expression. Mechanistic studies divulged that the p53/p21 pathway was involved in YPEL2-induced cellular senescence. We conclude that YPEL2 promotes cellular senescence via the p53/p21 pathway and that YPEL2 expression is elevated in atherosclerosis. These findings reveal YPEL2 as a potential therapeutic target in aging-associated diseases.

A Novel Mitochondrial-Related Gene Signature for the Tumor Immune Microenvironment Evaluation and Prognosis Prediction in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. More and more studies have reported that mitochondrial-related genes (MTRGs) were associated with the clinical outcomes of multiple tumors solely. In this study, we aimed to develop a novel prognostic model based on MTRGs. Differentially expressed MTRGs were identified from TCGA-LUAD and GSE31210 cohorts. Univariate Cox regression analysis was utilized to screen differentially expressed MTRGs that were related to prognosis of LUAD. Then, LASSO Cox regression analysis was used to develop a prognostic signature. ESTIMATE was used for estimating the fractions of immune cell types. In this study, we identified 44 overlapping differentially expressed MTRGs in TCGA-LUAD and GSE31210 cohorts. Among 44 overlapping differentially expressed MTRGs, nine genes were associated with prognosis of LUAD. When the penalty parameter lambda was the minimum, there were six genes meeting the conditions of constructing the signature, including SERPINB5, CCNB1, FGR MAOB, SH3BP5, and CYP24A1. The survival analysis suggested that prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. Cox regression analyses showed that the risk score was an independent predictor of LUAD prognosis. As with the results of ESTIMATE score, the degree of immune cell infiltration in the low-risk group was higher than that in the high-risk group, such as TIL, Treg, and B cells. In addition, TMB and cancer stem cell infiltration were higher in the low-risk group than the high-risk group. In conclusion, we developed a novel MTRG signature acting as a negative independent prognostic factor. In the future, individualized treatments and medical decision-making may benefit from using the predicted model.