Scaling of the strange-metal scattering in unconventional superconductors.

Marked evolution of properties with minute changes in the doping level is a hallmark of the complex chemistry that governs copper oxide superconductivity as manifested in the celebrated superconducting domes and quantum criticality taking place at precise compositions1-4. The strange-metal state, in which the resistivity varies linearly with temperature, has emerged as a central feature in the normal state of copper oxide superconductors5-9. The ubiquity of this behaviour signals an intimate link between the scattering mechanism and superconductivity10-12. However, a clear quantitative picture of the correlation has been lacking. Here we report the observation of precise quantitative scaling laws among the superconducting transition temperature (Tc), the linear-in-T scattering coefficient (A1) and the doping level (x) in electron-doped copper oxide La2-xCexCuO4 (LCCO). High-resolution characterization of epitaxial composition-spread films, which encompass the entire overdoped range of LCCO, has enabled us to systematically map its structural and transport properties with unprecedented accuracy and with increments of Δx = 0.0015. We have uncovered the relations Tc ~ (xc - x)0.5 ~ (A1□)0.5, where xc is the critical doping in which superconductivity disappears and A1□ is the coefficient of the linear resistivity per CuO2 plane. The striking similarity of the Tc versus A1□ relation among copper oxides, iron-based and organic superconductors may be an indication of a common mechanism of the strange-metal behaviour and unconventional superconductivity in these systems.

Integrated analysis of genome-wide association studies and 3D epigenomic characteristics reveal the BMP2 gene regulating loin muscle depth in Yorkshire pigs.

BACKGROUND: The lack of integrated analysis of genome-wide association studies (GWAS) and 3D epigenomics restricts a deep understanding of the genetic mechanisms of meat-related traits. With the application of techniques as ChIP-seq and Hi-C, the annotations of cis-regulatory elements in the pig genome have been established, which offers a new opportunity to elucidate the genetic mechanisms and identify major genetic variants and candidate genes that are significantly associated with important economic traits. Among these traits, loin muscle depth (LMD) is an important one as it impacts the lean meat content. In this study, we integrated cis-regulatory elements and genome-wide association studies (GWAS) to identify candidate genes and genetic variants regulating LMD. RESULTS: Five single nucleotide polymorphisms (SNPs) located on porcine chromosome 17 were significantly associated with LMD in Yorkshire pigs. A 10 kb quantitative trait locus (QTL) was identified as a candidate functional genomic region through the integration of linkage disequilibrium and linkage analysis (LDLA) and high-throughput chromosome conformation capture (Hi-C) analysis. The BMP2 gene was identified as a candidate gene for LMD based on the integrated results of GWAS, Hi-C meta-analysis, and cis-regulatory element data. The identified QTL region was further verified through target region sequencing. Furthermore, through using dual-luciferase assays and electrophoretic mobility shift assays (EMSA), two SNPs, including SNP rs321846600, located in the enhancer region, and SNP rs1111440035, located in the promoter region, were identified as candidate SNPs that may be functionally related to the LMD. CONCLUSIONS: Based on the results of GWAS, Hi-C, and cis-regulatory elements, the BMP2 gene was identified as an important candidate gene regulating variation in LMD. The SNPs rs321846600 and rs1111440035 were identified as candidate SNPs that are functionally related to the LMD of Yorkshire pigs. Our results shed light on the advantages of integrating GWAS with 3D epigenomics in identifying candidate genes for quantitative traits. This study is a pioneering work for the identification of candidate genes and related genetic variants regulating one key production trait (LMD) in pigs by integrating genome-wide association studies and 3D epigenomics.

Glucagon-like peptide-1 receptor agonist exendin 4 ameliorates diabetes-associated vascular calcification by regulating mitophagy through the AMPK signaling pathway.

BACKGROUND: Vascular calcification (VC) is a complication in diabetes mellitus (DM) patients. Osteogenic phenotype switching of vascular smooth muscle cells (VSMCs) plays a critical role in diabetes-related VC. Mitophagy can inhibit phenotype switching in VSMCs. This study aimed to investigate the role of the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin 4 (EX4) in mitophagy-induced phenotype switching. MATERIALS AND METHODS: The status of VC in T2DM mice was monitored using Von Kossa and Alizarin Red S (ARS) staining in mouse aortic tissue. Human aortic smooth muscle cells were cultured in high glucose (HG) and ß-glycerophosphate (ß-GP) conditioned medium. Accumulation of LC3B and p62 was detected in the mitochondrial fraction. The effect of EX4 in vitro and in vivo was investigated by knocking down AMPKα1. RESULTS: In diabetic VC mice, EX4 decreased the percentage of von Kossa/ARS positive area. EX4 inhibited osteogenic differentiation of HG/ß-GP-induced VSMCs. In HG/ß-GP-induced VSMCs, the number of mitophagosomes was increased, whereas the addition of EX4 restored mitochondrial function, increased the number of mitophagosome-lysosome fusions, and reduced p62 in mitochondrial frictions. EX4 increased the phosphorylation of AMPKα (Thr172) and ULK1 (Ser555) in HG/ß-GP-induced VSMCs. After knockdown of AMPKα1, ULK1 could not be activated by EX4. The accumulation of LC3B and p62 could not be reduced after AMPKα1 knockdown. Knockdown of AMPKα1 negated the therapeutic effects of EX4 on VC of diabetic mice. CONCLUSION: EX4 could promote mitophagy by activating the AMPK signaling pathway, attenuate insufficient mitophagy, and thus inhibit the osteogenic phenotype switching of VSMCs.

Anal intraepithelial neoplasia screening in women from the largest center for lower genital tract disease in China.

This study aimed to provide comprehensive clinical screening data for anal intraepithelial neoplasia (AIN). This study included 312 patients who underwent high-resolution anoscopy (HRA) examinations between January 1, 2020 and April 15, 2024. Clinical data, including demographic information, clinical history, cytology/high-risk human papilloma virus (hrHPV) results, and HRA records, were analyzed. The median age of all patients was 42 years (interquartile range: 33-52 years). Approximately 26.3% reported a history of VIN2/3+, 13.5% had a history of VaIN2/3+, 29.8% had a history of CIN2/3+, 44.6% had persistent cervical HPV16 infection, and 12.5% had immune suppression. Among the 312 patients, 14.4% were diagnosed with AIN2/3, 25.0% with AIN1 and 60.6% were normal. Anal cytological abnormalities were found in 41.3% of all patients, with a significantly higher rate in AIN2/3 patients than in ≤AIN1, 71.1% versus 36.3%, p < 0.001. The hrHPV positivity rate was 89.7%, with HPV16 being the most prevalent. The complete agreement rate for HRA impressions was 79.5%. Multi-variable analysis revealed immune suppression (odds ratio [OR]: 3.47, 95% confidence interval [CI]: 1.42-8.5) and VIN2/3+ (OR: 2.82, 95% CI: 1.27-6.28) were independent risk factors for AIN2/3. Abnormal cytology results (OR: 3.3, 95% CI: 1.52-7.17) and anal HPV16 infection (OR: 3.2, 95% CI: 1.26-8.12) demonstrated similar ORs for AIN2/3. Early screening for AIN2/3+ is crucial in Chinese women with lower genital tract precancerous and cancerous lesions, particularly in those with VIN2/3+ and immune suppression.

Using machine learning to realize genetic site screening and genomic prediction of productive traits in pigs.

Genomic prediction, which is based on solving linear mixed-model (LMM) equations, is the most popular method for predicting breeding values or phenotypic performance for economic traits in livestock. With the need to further improve the performance of genomic prediction, nonlinear methods have been considered as an alternative and promising approach. The excellent ability to predict phenotypes in animal husbandry has been demonstrated by machine learning (ML) approaches, which have been rapidly developed. To investigate the feasibility and reliability of implementing genomic prediction using nonlinear models, the performances of genomic predictions for pig productive traits using the linear genomic selection model and nonlinear machine learning models were compared. Then, to reduce the high-dimensional features of genome sequence data, different machine learning algorithms, including the random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost) and convolutional neural network (CNN) algorithms, were used to perform genomic feature selection as well as genomic prediction on reduced feature genome data. All of the analyses were processed on two real pig datasets: the published PIC pig dataset and a dataset comprising data from a national pig nucleus herd in Chifeng, North China. Overall, the accuracies of predicted phenotypic performance for traits T1, T2, T3 and T5 in the PIC dataset and average daily gain (ADG) in the Chifeng dataset were higher using the ML methods than the LMM method, while those for trait T4 in the PIC dataset and total number of piglets born (TNB) in the Chifeng dataset were slightly lower using the ML methods than the LMM method. Among all the different ML algorithms, SVM was the most appropriate for genomic prediction. For the genomic feature selection experiment, the most stable and most accurate results across different algorithms were achieved using XGBoost in combination with the SVM algorithm. Through feature selection, the number of genomic markers can be reduced to 1 in 20, while the predictive performance on some traits can even be improved compared to using the full genome data. Finally, we developed a new tool that can be used to execute combined XGBoost and SVM algorithms to realize genomic feature selection and phenotypic prediction.

Targeted versus Empiric Embolization for Delayed Postpancreatectomy Hemorrhage: A Retrospective Study of 312 Patients.

PURPOSE: To assess the safety and clinical effectiveness of empiric embolization (EE) compared with targeted embolization (TE) in the treatment of delayed postpancreatectomy hemorrhage (PPH). MATERIALS AND METHODS: The data of patients with delayed PPH between January 2012 and August 2022 were analyzed retrospectively. In total, 312 consecutive patients (59.6 years ± 10.8; 239 men) were included. The group was stratified into 3 cohorts according to angiographic results and treatment strategies: TE group, EE group, and no embolization (NE) group. The χ2 or Fisher exact test was implemented for comparing the clinical success and 30-day mortality. The variables related to clinical failure and 30-day mortality were identified by univariable and multivariable analyses. RESULTS: Clinical success of transcatheter arterial embolization was achieved in 70.0% (170/243) of patients who underwent embolization. There was no statistical difference in clinical success and 30-day mortality between the EE and TE groups. Multivariate analyses demonstrated that malignant disease (odds ratio [OR] = 5.76), Grade C pancreatic fistula (OR = 7.59), intra-abdominal infection (OR = 2.54), and concurrent extraluminal and intraluminal hemorrhage (OR = 2.52) were risk factors for clinical failure. Moreover, 33 patients (13.6%) died within 30 days after embolization. Advanced age (OR = 2.59) and intra-abdominal infection (OR = 5.55) were identified as risk factors for 30-day mortality. CONCLUSIONS: EE is safe and as effective as TE in preventing rebleeding and mortality in patients with angiographically negative delayed PPH.

Isolation and antioxidant activity of peptides from Chinese hairy tofu.

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.

Directional region-based feature point matching algorithm based on SURF.

Feature point matching is one of the fundamental tasks in binocular vision. It directly affects the accuracy and quality of 3D reconstruction. This study proposes a directional region-based feature point matching algorithm based on the SURF algorithm to improve the accuracy of feature point matching. First, same-name points are selected as the matching reference points in the left and right images. Then, the SURF algorithm is used to extract feature points and construct the SURF feature point descriptors. During the matching process, the location relationship between the query feature point and the reference point in the left image is directed to determine the corresponding matching region in the right image. Then, the matching is completed within this region based on Euclidean distance. Finally, the grid-based motion statistics algorithm is used to eliminate mismatches. Experimental results show that the proposed algorithm can substantially improve the matching accuracy and the number of valid matched points, particularly in the presence of a large amount of noise and interference. It also exhibits good robustness and stability.

The correlation between the level of cellular classification in bronchoalveolar lavage fluid of children with severe Mycoplasma pneumoniae and clinical characteristics.

Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infection disease in children. To date, there have been few studies on the relationship between cytological changes in bronchoalveolar lavage fluid (BALF) and clinical features. The objective of this study is to investigate the correlation between changes in the proportion of cell classifications in BALF and the clinical features in children with severe MPP (SMPP). In total, the study included 64 children with SMPP requiring bronchoalveolar lavage who were admitted to our hospital between March and September 2022 (study group) and 11 children with bronchial foreign bodies without co-infection (control group), who were admitted during the same period. The proportion of cell classifications in BALF was determined by microscopic examination after performing Wright-Giemsa staining. Patients were grouped according to different clinical characteristics, and between-group comparisons were made regarding the variations in the proportion of cell classifications in BALF. The levels of blood routine neutrophil percentage (GRA%), C-reactive protein, D-dimer and lactate dehydrogenase in the study group were higher than those in the control group (P < 0.05). There were differences in the GRA% and macrophage percentage in the BALF between the two groups (P < 0.05). The GRA% and blood lymphocyte percentage were associated with pleural effusion. Multiple indicators correlated with extrapulmonary manifestations (P < 0.05). Moreover, the percentage of lymphocytes in the BALF correlated with pleural effusion, extrapulmonary manifestations and refractory MPP (RMPP) (P < 0.05). Logistic regression showed that BALF lymphocytes were protective factors for RMPP, while serum amyloid A and extrapulmonary manifestations were risk factors (P < 0.05). CONCLUSION: The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. WHAT IS KNOWN: • Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. WHAT IS NEW: However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.

Anisodamine hydrobromide ameliorates acute lung injury via inhibiting pyroptosis in murine sepsis model.

OBJECTIVE: Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered ALI and elucidate the fundamental mechanisms involved. MATERIALS AND METHOD: The protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. RESULTS: Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1ß in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines. CONCLUSION: These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.

CircEML1 facilitates the steroid synthesis in follicular granulosa cells of chicken through sponging gga-miR-449a to release IGF2BP3 expression.

Non-coding RNAs (ncRNAs) induced competing endogenous RNAs (ceRNA) play crucial roles in various biological process by regulating target gene expression. However, the studies of ceRNA networks in the regulation of ovarian ovulation processing of chicken remains deficient compared to that in mammals. Our present study revealed that circEML1 was differential expressed in hen's ovarian tissues at different ages (15 W/20 W/30 W/68 W) and identified as a loop structure from EML1 pre-mRNA, which promoted the expressions of CYP19A1/StAR and E2/P4 secretion in follicular granulosa cells (GCs). Furthermore, circEML1 could serve as a sponge of gga-miR-449a and also found that IGF2BP3 was targeted by gga-miR-449a to co-participate in the steroidogenesis, which possibly act the regulatory role via mTOR/p38MAPK pathways. Meanwhile, in the rescue experiment, gga-miR-449a could reverse the promoting role of circEML1 to IGF2BP3 and steroidogenesis. Eventually, this study suggested that circEML1/gga-miR-449a/IGF2BP3 axis exerted an important role in the steroidogenesis in GCs of chicken.

An important issue of burnout among pre-hospital emergency medical personnel in Chengdu: a cross-sectional study.

OBJECTIVE: This survey aims to comprehensively understand occupational burnout among pre-hospital emergency medical personnel and explore associated risk factors. METHODS: A cross-sectional online survey using a census method was conducted between 15 July, 2023, and ends on 14 August, 2023, in Chengdu, SiChuan province, China. The questionnaire included general demographic information, the Maslach Burnout Inventory-General Survey (MBI-GS) with 15 items, and the Fatigue Scale-14 (FS-14) with 14 items. Univariate analysis was conducted on all variables, followed by multivariate logistic regression models to examine the associations between occupational burnout and the risk factors. RESULTS: A total of 2,299 participants,99.57% completed the survey effectively The participants were from 166 medical institutions in Chengdu, comprising 1,420 nurses (61.50%) and 889 clinical doctors (38.50%). A total of 33.36% participants experienced burnout, predominantly mild (30.27%), followed by moderate (2.78%) and severe (0.3%). Physicians, higher fatigue scores, age, work experience appeared to be related to burnout. Logistic regression models revealed that individuals aged over 50 were less prone to experience burnout compared to medical staff aged 18-30 (OR: 0.269, 95% CI: 0.115-0.627, p = 0.002). Physicians were more prone to experience burnout compared to nursing staff (OR: 0.690, 95% CI: 0.531-0.898, p = 0.006). Those with 0-5 years of experience were more prone to experience burnout compared to those with 6-10 years or over 15 years of experience (OR: 0.734, 95% CI: 0.547-0.986, p = 0.040; OR: 0.559, 95% CI: 0.339-0.924, p = 0.023). Additionally, for each 1-point increase in the fatigue score, the likelihood of burnout in medical staff increased by 1.367 times (OR: 1.367, 95% CI: 1.323-1.412, p < 0.0001). CONCLUSION: Pre-hospital emergency medical personnel demonstrate a notable prevalence of mild job burnout. These results provide a groundwork for future focus on the various stages of job burnout within pre-hospital emergency staff, alerting hospital and departmental managers to promptly address the mental well-being of their personnel and intervene as needed.

LncRNA lncLLM Facilitates Lipid Deposition by Promoting the Ubiquitination of MYH9 in Chicken LMH Cells.

The liver plays an important role in regulating lipid metabolism in animals. This study investigated the function and mechanism of lncLLM in liver lipid metabolism in hens at the peak of egg production. The effect of lncLLM on intracellular lipid content in LMH cells was evaluated by qPCR, Oil Red O staining, and detection of triglyceride (TG) and cholesterol (TC) content. The interaction between lncLLM and MYH9 was confirmed by RNA purification chromatin fractionation (CHIRP) and RNA immunoprecipitation (RIP) analysis. The results showed that lncLLM increased the intracellular content of TG and TC and promoted the expression of genes related to lipid synthesis. It was further found that lncLLM had a negative regulatory effect on the expression level of MYH9 protein in LMH cells. The intracellular TG and TC content of MYH9 knockdown cells increased, and the expression of genes related to lipid decomposition was significantly reduced. In addition, this study confirmed that the role of lncLLM is at least partly through mediating the ubiquitination of MYH9 protein to accelerate the degradation of MYH9 protein. This discovery provides a new molecular target for improving egg-laying performance in hens and treating fatty liver disease in humans.

Loss of microbial functional diversity following Spartina alterniflora invasion reduces the potential of carbon sequestration and nitrogen removal in mangrove sediments-from a gene perspective.

Mangrove ecosystems play an important role in carbon (C) sequestration and nitrogen (N) removal. Although Spartina alterniflora has successively invaded native mangrove habitats during the preceding two decades, the effects of this invasion on the microbial functional potential involved in nutrient cycling remain unclear. In this study, metagenomic sequencing was used to investigate microbial C and N cycling in sediments derived from S. alterniflora and three native mangrove species (Kandelia obovata, Avicennia marina, and Aegiceras corniculatum). Greater differences in functional profiles of C and N cycling-related genes were observed between S. alterniflora and mangrove sediments than between different mangrove sediments. Functional diversity was lower in S. alterniflora sediments than in native mangrove sediments. The growth of Thaumarchaeota and Proteobacteria, was enhanced due to their resilience to diversity loss, while the growth of oligotrophs, such as Chloroflexi and Firmicutes, was inhibited in S. alterniflora sediments. Compared to mangrove sediments, the abundance of genes involved in C fixation and methane production was lower in S. alterniflora sediments. However, S. alterniflora significantly increased the gene abundance of pmo which controlled the oxidation process of CH4 to carbon dioxide. Additionally, genes involved in nitrification were enriched, whereas genes involved in N reduction processes, such as denitrification and dissimilatory nitrate reduction to ammonium, N immobilization, and N mineralization, were depleted in S. alterniflora sediments compared to mangrove sediments. Partial least squares regression models demonstrated that the decrease in soil organic C and increase in pH after S. alterniflora invasion induced the loss of microbial functional diversity, which was the main driver of changes in the abundances of genes involved in C and N cycling. Overall, our findings indicate that S. alterniflora invasion modifies the microbial functional profile of nutrient cycling in native mangrove ecosystems and potentially weakens the capacity of mangroves to sequester carbon and remove nitrogen.

Evaluating effects of climate change on the spatial distribution of an atypical cavefish Onychostoma macrolepis.

Comprehending endangered species' spatial distribution in response to global climate change (GCC) is of great importance for formulating adaptive management, conservation, and restoration plans. However, it is regrettable that previous studies mainly focused on geoclimatic species, while neglected climate-sensitive subterranean taxa to a large extent, which clearly hampered the discovery of universal principles. In view of this, taking the endemic troglophile riverine fish Onychostoma macrolepis (Bleeker, 1871) as an example, we constructed a MaxEnt (maximum-entropy) model to predict how the spatial distribution of this endangered fish would respond to future climate changes (three Global Climate Models × two Shared Socio-economic Pathways × three future time nodes) based on painstakingly collected species occurrence data and a set of bioclimatic variables, including WorldClim and ENVIREM. Model results showed that variables related to temperature rather than precipitation were more important in determining the geographic distribution of this rare and endemic fish. In addition, the suitable areas and their distribution centroids of O. macrolepis would shrink (average: 20,901.75 km2) and move toward the northeast or northwest within the study area (i.e. China). Linking our results with this species' limited dispersion potential and unique habitat requirements (i.e. karst landform is essential), we thus recommended in situ conservation to protect this relict.

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A 70-year-old man had radical surgery for colon cancer one year before the symptoms of memory loss and decreasing cognitive function. Subsequent magnetic resonance imaging revealed a brain mass, which was surgically resected and confirmed to be metastatic intestinal adenocarcinoma. Immunohistochemistry of the primary tumor and brain metastasis showed mismatch repair deficiency. The patient received adjuvant chemotherapy after surgery. However, the brain metastasis relapsed one month after the last chemotherapy. Genetic testing on the resected colon tumor samples confirmed microsatellite instability-high with a high tumor mutation burden by 77.7 muts/Mb. The patient was subsequently treated with programmed death-1 (PD-1) monoclonal antibody pembrolizumab (keytruda). The brain metastatic lesions were completely shrunk, and a complete clinical response was achieved.

CDKN2B-AS1 mediates proliferation and migration of vascular smooth muscle cells induced by insulin.

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the intimal hyperplasia in type 2 diabetes mellitus (T2DM) patients after percutaneous coronary intervention. We aimed to investigate the role of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in VSMC proliferation and migration, as well as the underlying mechanism. T2DM model mice with carotid balloon injury were used in vivo and mouse aortic vascular smooth muscle cells (MOVAS) stimulated by insulin were used in vitro to assess the role of CDKN2B-AS1 in VSMC proliferation and migration following vascular injury in T2DM state. To investigate cell viability and migration, MTT assay and Transwell assay were conducted. To elucidate the underlying molecular mechanisms, the methylation-specific polymerase chain reaction, RNA immunoprecipitation, RNA-pull down, co-immunoprecipitation, and chromatin immunoprecipitation were performed. In vivo, CDKN2B-AS1 was up-regulated in common carotid artery tissues. In vitro, insulin treatment increased CDKN2B-AS1 level, enhanced MOVAS cell proliferation and migration, while the promoting effect was reversed by CDKN2B-AS1 knockdown. CDKN2B-AS1 forms a complex with enhancer of zeste homolog 2 (EZH2) and DNA methyltransferase (cytosine-5) 1 (DNMT1) to regulate smooth muscle 22 alpha (SM22α) methylation levels. In insulin-stimulated cells, SM22α knockdown abrogated the inhibitory effect of CDKN2B-AS1 knockdown on cell viability and migration. Injection of lentivirus-sh-CDKN2B-AS1 relieved intimal hyperplasia in T2DM mice with carotid balloon injury. Up-regulation of CDKN2B-AS1 induced by insulin promotes cell proliferation and migration by targeting SM22α through forming a complex with EZH2 and DNMT1, thereby aggravating the intimal hyperplasia after vascular injury in T2DM.

Intermediate-Term Prognostic Value of Homocysteine in Acute Coronary Syndrome Complicated with or without Hypertension: A Multicenter Observational Cohort Study.

Background: As a classical biomarker associated with hypertension, the prognostic value of homocysteine (Hcy) in the intermediate-term outcome of acute coronary syndrome (ACS) remains controversial. This study aimed to investigate the role of homocysteine in ACS patients with different blood pressure statuses. Methods: A total of 1288 ACS patients from 11 general hospitals in Chengdu, China, from June 2015 to December 2019 were consecutively included in this observational study. The primary endpoint was defined as all-cause death. Secondary endpoints included cardiac death, nonfatal myocardial infarction (MI), unplanned revascularization and nonfatal stroke. The patients in the hypertension group (n = 788) were further stratified into hyperhomocysteinemia (H-Hcy, n = 245) and normal homocysteinaemia subgroups (N-Hcy, n = 543) around the cut-off value of 16.81 µmol/L. Similarly, the nonhypertensive patients were stratified into H-Hcy (n = 200) and N-Hcy subgroups (n = 300) around the optimal cut-off value of 14.00 µmol/L. The outcomes were compared between groups. Results: The median follow-up duration was 18 months. During this period, 78 (6.05%) deaths were recorded. Kaplan‒Meier curves illustrated that H-Hcy had a lower survival probability than N-Hcy in both hypertension and nonhypertension groups (p < 0.01). Multivariate Cox regression analysis revealed that H-Hcy was a predictor of intermediate-term mortality in ACS, regardless of blood pressure status. Conclusions: Elevated Hcy levels predict intermediate-term all-cause mortality in ACS regardless of blood pressure status. This association could be conducive to risk stratification of ACS. Clinical Trial Registration: The study was registered in the Chinese Clinical Trials Registry in China (ChiCTR1900025138).

Sialic Acid Enhanced the Antistress Capability under Challenging Situations by Increasing Synaptic Transmission.

BACKGROUND: In early life, sialic acid (SA) plays a crucial role in neurodevelopment and neuronal function. However, it remains unclear whether and how SA supplementation in early life promotes behavioral response to stress in adolescence. OBJECTIVES: This study aimed to examine the effects and mechanisms of SA on the antistress capability under challenging situations. METHODS: In this study, C57BL/6 mice were daily supplemented with 1 µL SA solution/g body weight at the dose of 10 mg/kg/d from postnatal day (PND) 5-45. The antistress behaviors, including open field, elevated plus maze, forced swimming test, and tail suspension test, were performed at PND 46, PND 48, PND 50, and PND 52 to detect the antistress ability of SA, respectively. RESULTS: Our results showed that SA-treated mice were more active in facing challenging situations. The fiber photometry experiment showed that SA promoted the excitatory neuronal response in the medial prefrontal cortex (mPFC), which was extensively interconnected to stress. Besides, electrophysiological results revealed SA enhanced synaptic transmission rather than neuronal excitability of mPFC excitatory neurons. It was also supported by the increasing spine density of mPFC excitatory neurons. At the molecular amount, the SA elevated the transmitter release-related proteins of mPFC, including Synapsin 1 and vesicular glutamate transporter 1 (VGlut 1). Furthermore, SA supplementation enhanced synaptic transmission mainly by altering the kinetics of synaptic transmission. CONCLUSIONS: The SA supplementation enhanced the response capability to stress under challenging situations, and the enhanced synaptic transmission of mPFC excitatory neurons may be the neurological basis of active response under challenging situations. In general, our findings suggested that SA supplementation in early life can promote stress resistance in adolescence.