Geographic differences in pharmacotherapy patterns and outcomes of acute ischemic stroke in China.

BACKGROUND: Vast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care. METHODS: This study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015-2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3-6 was assessed at 3 and 12 months. Multivariate logistic regression was used. RESULTS: Among 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53-3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38-0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05). CONCLUSIONS: There was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT02470624).

Aquaporin 4 Mediates the Effect of Iron Overload on Hydrocephalus After Intraventricular Hemorrhage.

BACKGROUND: Iron overload plays an important role in hydrocephalus development following intraventricular hemorrhage (IVH). Aquaporin 4 (AQP4) participates in the balance of cerebrospinal fluid secretion and absorption. The current study investigated the role of AQP4 in the formation of hydrocephalus caused by iron overload after IVH. METHODS: There were three parts to this study. First, Sprague-Dawley rats received an intraventricular injection of 100 µl autologous blood or saline control. Second, rats had IVH and were treated with deferoxamine (DFX), an iron chelator, or vehicle. Third, rats had IVH and were treated with 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), a specific AQP4 inhibitor, or vehicle. Rats underwent T2-weighted and T2* gradient-echo magnetic resonance imaging to assess lateral ventricular volume and intraventricular iron deposition at 7, 14, and 28 days after intraventricular injection and were then euthanized. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence analyses were conducted on the rat brains to evaluate the expression of AQP4 at different time points. Hematoxylin and eosin-stained brain sections were obtained to assess the ventricular wall damage on day 28. RESULTS: Intraventricular injection of autologous blood caused a significant ventricular dilatation, iron deposition, and ventricular wall damage. There was increased AQP4 mRNA and protein expression in the periventricular tissue in IVH rats through day 7 to day 28. The DFX treatment group had a lower lateral ventricular volume and less intraventricular iron deposition and ventricular wall damage than the vehicle-treated group after IVH. The expression of AQP4 protein in periventricular tissue was also inhibited by DFX on days 14 and 28 after IVH. The use of TGN-020 attenuated hydrocephalus development after IVH and inhibited the expression of AQP4 protein in the periventricular tissue between day 14 and day 28 without a significant effect on intraventricular iron deposition or ventricular wall damage. CONCLUSIONS: AQP4 located in the periventricular area mediated the effect of iron overload on hydrocephalus after IVH.

Prediagnosis ultra-processed food consumption and prognosis of patients with colorectal, lung, prostate, or breast cancer: a large prospective multicenter study.

Background and aims: Whether ultra-processed food consumption is associated with cancer prognosis remains unknown. We aimed to test whether prediagnosis ultra-processed food consumption is positively associated with all-cause and cancer-specific mortality in patients with colorectal, lung, prostate, or breast cancer. Methods: This study included 1,100 colorectal cancer patients, 1750 lung cancer patients, 4,336 prostate cancer patients, and 2,443 breast cancer patients. Ultra-processed foods were assessed using the NOVA classification before the diagnosis of the first cancer. Multivariable Cox regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cancer-specific mortality. Results: High ultra-processed food consumption before cancer diagnosis was significantly associated with an increased risk of all-cause mortality in lung (HRquartile 4 vs. 1: 1.18; 95% CI: 0.98, 1.40; Ptrend = 0.021) and prostate (HRquartile 4 vs. 1: 1.18; 95% CI: 1.00, 1.39; Ptrend = 0.017) cancer patients in a nonlinear dose-response manner (all Pnonlinearity < 0.05), whereas no significant results were found for other associations of interest. Subgroup analyses additionally revealed a significantly positive association with colorectal cancer-specific mortality among colorectal cancer patients in stages I and II but not among those in stages III and IV (Pinteraction = 0.006), and with prostate cancer-specific mortality among prostate cancer patients with body mass index <25 but not among those with body mass index ≥25 (Pinteraction = 0.001). Conclusion: Our study suggests that reducing ultra-processed food consumption before cancer diagnosis may improve the overall survival of patients with lung or prostate cancer, and the cancer-specific survival of certain subgroups of patients with colorectal or prostate cancer.

The relationship between hematoma morphology and intraventricular hemorrhage in supratentorial deep intracerebral hemorrhage.

Background: Intraventricular hemorrhage (IVH) after intracerebral hemorrhage (ICH) is a strong independent predictor of poor outcomes. Although the location and volume of ICH are associated with IVH, our knowledge concerning the mechanism of IVH after ICH is still limited. This study aimed to investigate the relationship between hematoma morphology and IVH in patients with supratentorial deep ICH. Methods: We retrospectively analyzed adult patients (aged ≥18 years) with spontaneous supratentorial deep ICH who underwent computed tomography (CT) within 48 h after ICH symptom onset in Peking University First Hospital between January 2017 and August 2022. We collected the clinical and imaging data of the patients and assessed hematoma morphology using several quantitative radiological parameters including hematoma volume, sphericity index, A/B ratio (A: the largest area of hematoma; B: the largest diameter 90° to A on the same slice), and our newly proposed largest diameter-midline angle (LMA). Multivariable logistic regression analysis was used to analyze the relationship between these parameters and the presence of IVH on the initial CT scan. Results: Among 114 patients with spontaneous supratentorial deep ICH, 41 (36.0%) had IVH. In patients with IVH, the sphericity index was lower than that in individuals without IVH, while the LMA was larger. Multivariate logistic regression analysis showed that sphericity index [0.1-unit odds ratio (OR) =0.252; 95% CI: 0.089-0.709; P=0.009] and the LMA (10-unit OR =1.281; 95% CI: 1.007-1.630; P=0.04) were independently associated with the presence of IVH in patients with supratentorial deep ICH. Univariate analyses showed that hematoma volume, A/B ratio, sphericity index, and the LMA were significantly associated with poor outcomes at discharge. Conclusions: Two quantitative parameters of hematoma morphology, sphericity index and the LMA, were significantly associated with the presence of IVH in patients with supratentorial deep ICH. Further prospective studies with larger sample sizes are needed to validate our results.

Epilepsy in a Patient With Brain Herniation Into the Arachnoid Granulation.

This case report describes epilepsy in a 50-year-old patient with brain herniation into the arachnoid granulation.

Circular RNA circBLNK promotes osteosarcoma progression and inhibits ferroptosis in osteosarcoma cells by sponging miR­188­3p and regulating GPX4 expression.

As a newly identified circular RNA (circRNA), the role of circBLNK in cancer progression has not been probed. The objective of the present study was to functionally dissect the role of circBLNK in osteosarcoma (OS) tumorigenesis and progression. With regards of the experimental procedure, the levels of mRNAs and proteins were assessed using reverse transcription­quantitative PCR and western blot analysis, respectively. The subcellular location of circBLNK in OS cells was determined by cell cytosolic/nuclear fractionation assay. Cell ferroptosis ability was assessed through MTT assay. Cell proliferative abilities were assessed by clonogenic and Cell Counting Kit­8 assays, and cell apoptosis was measured using flow cytometry. The relationships among circBLNK, miR­188­3p, and glutathione peroxidase 4 (GPX4) were validated by luciferase reporter and RNA pull­down assays, as well as RNA immunoprecipitation. The stability of circBLNK and linear BLNK was confirmed using RNase R treatment assay. The association between circBLNK expression and overall survival rate was assessed by Kaplan­Meier plot. The correlation between the expression levels of circBLNK, miR­188­3p, and GPX4 in OS tissues was assessed by Pearson's χ2 test. The results revealed that CircBLNK and GPX4 were significantly upregulated in OS tissues, which predicted the poor prognosis. CircBLNK knockdown led to suppressed cell proliferation and enhanced cell apoptosis, an effect that could be reversed by the inhibition of miR­188­3p. In an in vivo circBLNK deficiency model, tumor growth was observed to be markedly suppressed. Moreover, circBLNK deficiency elevated levels of intracellular free iron (Fe2+), malondialdehyde, lipid reactive oxygen species and mitochondrial superoxide, while diminishing mitochondrial membrane potential in Erastin­treated OS cells, which were eliminated by overexpressing GPX4. Furthermore, mechanistic investigations revealed that circBLNK sponged miR­188­3p to regulate the expression of GPX4, thereby affecting OS progression. In conclusion, the present study delineated a new regulatory axis involving circBLNK/miR­188­3p/GPX4 in OS progression, adding to the growing evidence that circRNAs are critical gene regulators in cancer progression.

Clinical characteristics and acute complication of COVID-19 patients with diabetes: a multicenter, retrospective study in Southern China.

Aims: This study aims to describe the clinical characteristics, laboratory data and complications of hospitalized COVID-19 patients with type 2 diabetes mellitus (T2DM) since epidemic prevention and control optimization was adjusted in December 2022 in China. Methods: This retrospective multicenter study included 298 patients with confirmed type 2 diabetes mellitus with or without COVID-19. We collected data from the first wave of the pandemic in The Fifth Affiliated Hospital of Guangzhou Medical University, Loudi Central Hospital and The First People's Hospital of Xiangtan from December 1, 2022 to February 1, 2023. We extracted baseline data, clinical symptoms, acute complications, laboratory findings, treatment and outcome data of each patient from electronic medical records. Results: For among 298 hospitalized patients with type 2 diabetes, 136 (45.6%) were COVID-19 uninfected, and 162 (54.4%) were COVID-19 infected. We found that the incidence of cough, fatigue, fever, muscle soreness, sore throat, shortness of breath, hyposmia, hypogeusia and polyphagia (all p<0.01) were significantly higher in the exposure group. They showed higher levels of ketone (p=0.04), creatinine (p<0.01), blood potassium (p=0.01) and more diabetic ketoacidosis (p<0.01). Patients with COVID-19 less use of metformin (p<0.01), thiazolidinediones (p<0.01) and SGLT2 (p<0.01) compared with patients without COVID-19. Conclusion: COVID-19 patients with diabetes showed more severe respiratory and constitutional symptoms and an increased proportion of hyposmia and hypogeusia. Moreover, COVID-19 patients with diabetes have a higher incidence of acute complications, are more prone to worsening renal function, and are more cautious about the use of antidiabetic drugs.

Glycopeptide database search and de novo sequencing with PEAKS GlycanFinder enable highly sensitive glycoproteomics.

Here we present GlycanFinder, a database search and de novo sequencing tool for the analysis of intact glycopeptides from mass spectrometry data. GlycanFinder integrates peptide-based and glycan-based search strategies to address the challenge of complex fragmentation of glycopeptides. A deep learning model is designed to capture glycan tree structures and their fragment ions for de novo sequencing of glycans that do not exist in the database. We performed extensive analyses to validate the false discovery rates (FDRs) at both peptide and glycan levels and to evaluate GlycanFinder based on comprehensive benchmarks from previous community-based studies. Our results show that GlycanFinder achieved comparable performance to other leading glycoproteomics softwares in terms of both FDR control and the number of identifications. Moreover, GlycanFinder was also able to identify glycopeptides not found in existing databases. Finally, we conducted a mass spectrometry experiment for antibody N-linked glycosylation profiling that could distinguish isomeric peptides and glycans in four immunoglobulin G subclasses, which had been a challenging problem to previous studies.

Early cerebral hemodynamic changes following unilateral carotid artery stenting in patients with different degrees of carotid stenosis.

Background: Few studies have focused on cerebral hemodynamics in the early stage following carotid artery stenting (CAS). This retrospective cohort study aimed to investigate cerebral hemodynamic changes within 6 hours of unilateral CAS in patients with different degrees of carotid stenosis. Methods: A total of 104 patients who underwent CAS accompanied by transcranial color-code Doppler or transcranial Doppler were enrolled in the study. The participants were divided into the following 3 groups based on the degree of carotid stenosis: severe stenosis group, extreme stenosis group, and near occlusion group. Bilateral middle cerebral artery (MCA) peak systolic velocity (PSV) and pulsatility index (PI) were measured using transcranial color-code Doppler before and 1 and 3 hours following CAS. Blood pressure, MCA-PSV, and PI were compared among the 3 groups. Results: At 1 hour following CAS, ipsilateral MCA-PSV increased compared to the baseline in the severe stenosis group [84±21 vs. 93±27 cm/s; 8.1%; interquartile range (IQR), 1.4-20.1%; P<0.001]. A similar hemodynamic change, but of a larger magnitude, was observed in the extreme stenosis group (83±24 vs. 100±29 cm/s; 20.8%; IQR, 5.3-33.1%; P<0.001) and near occlusion group (73±24 vs. 109±29 cm/s, 45.8%; IQR, 24.3-73.1%; P<0.001). At 3 hours after CAS, the hemodynamic changes were the same as those at 1 hour. PI increased in all 3 groups following CAS. A subgroup analysis was performed according to symptoms, sex, smoking status, history of hypertension, and presence of hyperlipidemia or diabetes, and the increase in ipsilateral MCA-PSV was not significant. In terms of adverse events, only 4 patients in the near occlusion group experienced transient post-CAS hyperperfusion. Conclusions: The ipsilateral MCA-PSV and PI in patients following unilateral CAS increased significantly in the initial hours. The increase in ipsilateral MCA-PSV was considerably higher in patients with a severe degree of stenosis. Near occlusion of the carotid artery was an independent risk factor for hyperperfusion after unilateral CAS.

Tumor-associated macrophages mediate gastrointestinal stromal tumor cell metastasis through CXCL2/CXCR2.

BACKGROUND: Tumor-associated macrophages (TAMs) are linked with the progression and poor prognosis of multifarious solid tumors, but the regulatory mechanisms involved in gastrointestinal stromal tumors (GIST) remain indistinct. This study intended to delve into the job of TAM-derived chemokines in promoting metastasis in GIST microenvironment. METHODS: Expression levels of M2-TAM markers and CXCL2 in primary and metastatic tissues of GIST were analyzed by bioinformatics methods, and we analyzed the correlation between CXCL2 and M2-TAM markers. Immunofluorescence was applied to assay CXCL2 and M2-TAM marker protein (CD68 and CD206) expression in tumor tissues. Serum CXCL2 concentration in metastatic and non-metastatic patients was assayed by ELISA. The differentiation of THP-1 cells was tested by flow cytometry. Cell function test was utilized to analyze the viability, invasion and migration of GIST cells. Western blot was used to examine the expression of epithelial-mesenchymal transition (EMT)-related proteins. The mouse liver metastasis model was established, and the effects of CXCL2 and EMT-related genes on metastasis were confirmed by hematoxylin-eosin staining and immunohistochemistry experiments. RESULTS: Bioinformatics analysis ascertained that M2-TAM marker proteins and chemokine CXCL2 were highly expressed in GIST metastatic tissues, and CXCL2 and TAM were co-located in tumor tissues. Results of in vitro cell function experiments displayed that CXCL2 secreted by M2-TAM promoted the invasion, migration and EMT of GIST tumor cells, and the anti-CXCL2 antibody could block the metastasis promoting effect of CXCL2. Additionally, the silencing of CXCR2 in GIST cells inhibited the metastasis promoting effect of CXCL2. Animal studies further confirmed that CXCL2 promoted liver metastasis of GIST in vivo. CONCLUSION: This study preliminarily revealed the mechanism of M2-TAM promoting tumor metastasis by secreting CXCL2 in GIST tumor microenvironment, and proffered theoretical reference for the development of immunotherapy strategies targeting M2-TAM.

Ultra-processed food consumption and the risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Whether ultra-processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population-based cohort of 98 265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow-up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra-processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1 :1.49; 95% confidence interval [CI]: 1.07-2.07; Ptrend  = .021) in a linear dose-response manner (Pnonlinearity  = .075). Subgroup analysis further found that the positive association of ultra-processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1 :2.17; 95% CI: 1.14-4.15) than in those aged ≥65 years (HRquartile 4 vs 1 :1.32; 95% CI: 0.88-1.94), though the interaction test failed to achieve the statistical significance (Pinteraction  = .061). These findings suggest that reducing ultra-processed food consumption may be beneficial in decreasing pancreatic cancer incidence.

Elevated tissue inhibitor of metalloproteinase-1 along with left atrium hypertrophy predict atrial fibrillation recurrence after catheter ablation.

This study aimed to establish a model that predicts atrial fibrillation (AF) recurrence after catheter ablation using clinical risk factors and biomarkers. We used a prospective cohort study, including 230 consecutive persistent AF patients successfully treated with catheter ablation from January 2019 to December 2020 in our hospital. AF recurrence was followed-up after catheter ablation, and clinical risk factors and biomarkers for AF recurrence were analyzed. AF recurred after radiofrequency ablation in 72 (31%) patients. Multiple multivariate logistic regression analysis demonstrated that tissue inhibitor of metalloproteinase-1 (TIMP-1) and left atrium diameter (LAd) were closely associated with AF recurrence. The prediction model constructed by combining TIMP-1 and LAd effectively predicted AF recurrence. Additionally, the model's performance discrimination, accuracy, and calibration were confirmed through internal validation using bootstrap resampling (1,000 times). The model showed good fitting (Hosmer-Lemeshow goodness chi-square 3.76138, p = 0.926) and had a superior discrimination ability (the area under the receiver operation characteristic curve0.917; 95% CI 0.882-0.952). The calibration curve showed good agreement between the predicted probability and the actual probability. Moreover, the decision curve analysis (DCA) showed the clinical useful of the nomogram. In conclusion, our predictive model based on serum TIMP-1 and LAd levels could predict AF recurrence after catheter ablation.

m6A and miRNA jointly regulate the development of breast muscles in duck embryonic stages.

N6-methyladenosine (m6A) is an abundant internal mRNA modification and plays a crucial regulatory role in animal growth and development. In recent years, m6A modification has been found to play a key role in skeletal muscles. However, whether m6A modification contributes to embryonic breast muscle development of Pekin ducks has not been explored. To explore the role of m6A in embryonic breast muscle development of ducks, we performed m6A sequencing and miRNA sequencing for the breast muscle of duck embryos on the 19th (E19) and 27th (E27) days. A total of 12,717 m6A peaks were identified at E19, representing a total of 7,438 gene transcripts. A total of 14,703 m6A peaks were identified, which overlapped with the transcripts of 7,753 genes at E27. Comparing E19 and E27, we identified 2,347 differential m6A peaks, which overlapped with 1,605 m6A-modified genes (MMGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that MMGs were enriched in multiple muscle- or fat-related pathways, which was also revealed from our analysis of differentially expressed genes (DEGs). Conjoint analysis of m6A-seq and RNA-seq data showed that pathways related to ß-oxidation of fatty acids and skeletal muscle development were significantly enriched, suggesting that m6A modification is involved in the regulation of fat deposition and skeletal muscle development. There were 90 upregulated and 102 downregulated miRNAs identified between the E19 and E27 stages. Through overlapping analysis of genes shared by MMGs and DEGs and the targets of differentially expressed miRNAs (DEMs), we identified six m6A-mRNA-regulated miRNAs. Finally, we found that m6A modification can regulate fat deposition and skeletal muscle development. In conclusion, our results suggest that m6A modification is a key regulator for embryonic breast muscle development and fat deposition of ducks by affecting expressions of mRNAs and miRNAs. This is the first study to comprehensively characterize the m6A patterns in the duck transcriptome. These data provide a solid basis for future work aimed at determining the potential functional roles of m6A modification in adipose deposition and muscle growth.

Higher serum tissue inhibitor of metalloproteinase-1 predicts atrial fibrillation recurrence after radiofrequency catheter ablation.

Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) levels is strongly associated with cardiac extracellular matrix accumulation and atrial fibrosis. Whether serum levels of TIMP-1 are associated with atrial fibrillation (AF) recurrence following radiofrequency catheter ablation (RFCA) remains unknown. Materials and methods: Serum TIMP-1 levels of patients with AF before they underwent initial RFCA were measured using ELISA. Univariate and multivariate-adjusted Cox models were constructed to determine the relationship between TIMP-1 levels and AF recurrence. Multivariate logistic regression analyses were performed to determine predictors of AF recurrence. Results: Of the 194 enrolled patients, 61 (31.4%) had AF recurrence within the median 30.0 months (interquartile range: 16.5-33.7 months) of follow-up. These patients had significantly higher baseline TIMP-1 levels than those without AF recurrence (129.8 ± 65.7 vs. 112.0 ± 51.0 ng/ml, P = 0.041). The same was true of high-sensitivity C-reactive protein (3.9 ± 6.0 vs. 1.9 ± 2.8 ng/ml, P = 0.001). When a TIMP-1 cutoff of 124.15 ng/ml was set, patients with TIMP-1 ≥ 124.15 ng/ml had a higher risk of recurrent AF than those with TIMP-1 < 124.15 ng/ml (HR, 1.961, 95% CI, 1.182-2. 253, P = 0.009). Multivariate Cox regression analysis revealed that high TIMP-1 was an independent risk factor for AF recurrence. Univariate Cox regression analysis found that substrate modification surgery does not affect AF recurrence (P = 0.553). Subgroup analysis revealed that female sex, age < 65 years, hypertension (HTN), body mass index (BMI) ≥ 24 kg/m2, CHA2DS2-VASc score < 2, HAS-BLED score < 3, and EHRA score = 3 combined with high TIMP-1 level would perform well at predicting AF recurrence after RFCA. Conclusion: Elevated preoperative TIMP-1 levels are related to a higher risk of AF recurrence and can independently predict AF recurrence following RFCA.

Integrated analysis of lncRNA and gene expression in longissimus dorsi muscle at two developmental stages of Hainan black goats.

It is deemed that meat quality of kids' is better than that of adults' for Hainan black goat. Generally, meat quality is affected by many indicators, such as intramuscular fat (IMF) content, muscle fiber diameter and shear force. It is indicated that long non-coding RNAs (lncRNAs) play essential roles in meat quality of goats. However, it is unclear whether and how lncRNAs and genes play their roles in meat quality of Hainan Black goats. Here, we firstly compared the meat quality between two-month-old kids (kids) and adult goats (adults). Then, the lncRNA-seq and RNA-seq data were integrated and analyzed to explore the potential functions of lncRNAs and genes. The results showed that adults' IMF content and muscle fiber diameter were extremely significantly higher than that of kids (P<0.01). For the sequenced data, average 84,970,398, and 83,691,250 clean reads were obtained respectively for Kids and adults, among which ~96% were mapped to the reference genome of goats. Through analyzing, 18,242 goat annotated genes, 1,429 goat annotated lncRNAs and 2,967 novel lncRNAs were obtained. Analysis of differential expression genes (DEGs) and lncRNAs (DELs) showed that 328 DEGs and 98 DELs existed between kids and adults. Furthermore, functional enrichment analysis revealed that a number of DEGs and DELs were mainly associated with IMF. Primarily, DGAT2 expressed higher in adults than that in kids and CPT1A expressed higher in kids than that in adults. Both of them were overlapped by DEGs and targets of DELs, suggesting the two DEGs and the DELs targeted by the two DEGs might be the potential regulators of goat IMF deposition. Taken together, our results provide basic support for further understanding the function and mechanism of lncRNAs and genes in meat quality of Hainan black goats.

Clinical and Laboratory Biomarkers in Paroxysmal Atrial Fibrillation: A Single Center Cross-Sectional Study.

The clinical risk profile of paroxysmal atrial fibrillation (pAF) patients is inconclusive. We aimed to identify clinical and laboratory biomarkers in patients with pAF and the differences in biomarkers among genders. A cross-sectional study was conducted with a total of 181 participants in a single center in Beijing Anzhen Hospital. The participants were grouped according to the presence of pAF and sex differences, and clinical and laboratory results were collected and compared. The 181 participants had a mean age of 52.9 ± 15.1 years (pAF group, 60.4 ± 9.9 years, SR group, 48.3 ± 15.9 years, P < 0.05). Patients with pAF had significantly higher rates of age, left atrial (LA) diameter, haemoglobin (Hb) levels, tissue inhibitor of metalloproteinase-1 (TIMP-1), soluble tumour suppressor-2 (sST2), B-type natriuretic peptide (BNP) and indirect bilirubin (Ibil), mean haemoglobin concentration (MCHC), and hypertension (HTN) and smoking (P < 0.05). Multivariable logistic regression analysis revealed that age (OR = 1.075, 95% CI: 1.035-1.118, P < 0.0001), smoking (OR = 4.538, 95% CI: 1.559-13.205, P = 0.006), and MCHC (OR = 1.062, 95% CI: 1.019-1.106, P = 0.004) were independent predictive factors for pAF. Multivariable logistic regression analysis found that age (OR = 1.107, 95% CI: 1.016-1.206, P = 0.02) and Ibil level (OR = 2.303, 95% CI: 1.158-4.582, P = 0.017) were independent predictive factors of the occurrence of pAF in females; BNP (OR = 1.015, 95% CI: 1.002-1.029, P = 0.029) was an independent predictive variable of pAF in males. Age, smoking, and MCHC were independent predictive factors of pAF. BNP was an independent predictive biomarker of pAF in males, while in females, age and Ibil were independent predictive factors.

The MFN1 and MFN2 mitofusins promote clustering between mitochondria and peroxisomes.

Mitochondria and peroxisomes are two types of functionally close-related organelles, and both play essential roles in lipid and ROS metabolism. However, how they physically interact with each other is not well understood. In this study, we apply the proximity labeling method with peroxisomal proteins and report that mitochondrial protein mitofusins (MFNs) are in proximity to peroxisomes. Overexpression of MFNs induces not only the mitochondria clustering but also the co-clustering of peroxisomes. We also report the enrichment of MFNs at the mitochondria-peroxisome interface. Induced mitofusin expression gives rise to more mitochondria-peroxisome contacting sites. Furthermore, the tethering of peroxisomes to mitochondria can be inhibited by the expression of a truncated MFN2, which lacks the transmembrane region. Collectively, our study suggests MFNs as regulators for mitochondria-peroxisome contacts. Our findings are essential for future studies of inter-organelle metabolism regulation and signaling, and may help understand the pathogenesis of mitofusin dysfunction-related disease.

Influence of Capture Selectivity and Left Intrahisian Block on QRS Characteristics During Left Bundle Branch Pacing.

OBJECTIVES: This study sought to examine QRS and intracardiac characteristics during selective (S) and nonselective (NS) left bundle branch pacing (LBBP) from direct left septal recordings. BACKGROUND: Criteria for S-LBBP and NS-LBBP have not been validated with intracardiac mapping. METHODS: Pacing was performed from multielectrode Purkinje recordings below the left-sided His. S-LBBP and NS-LBBP were performed in patients with narrow QRS (n = 9), right bundle branch block (n = 3), intraventricular conduction delay (n = 5), and left bundle branch block (n = 10). QRS duration was measured from stimulus onset (QRSst) and from the intrinsicoid deflection of the R-wave in V1-V2 (QRSid) to QRS end. Retrograde left bundle branch conduction was assessed by stimulus-to-retrograde His intervals. RESULTS: Among 27 patients analyzed, 20 demonstrated both NS- and S-LBBP and were studied in paired comparisons. NS-LBBP resulted in narrower QRS compared to S-LBBP (QRSst: 163 ms [interquartile range (IQR): 144-179 ms] vs 181 ms [IQR: 173-203 ms]; P < 0.001; QRSid: 125 ms [IQR: 117-142 ms] vs 150 ms [IQR: 135-157 ms]; P < 0.001). Left ventricular activation time was also significantly shorter for NS-LBBP compared to S-LBBP (88 ms [IQR: 75-111 ms] vs 97 ms [IQR: 82-123 ms]; P = 0.019). Left intrahisian block was bidirectional in 10 patients with long retrograde stimulus-to-His intervals. QRSst duration was significantly longer in patients with complete conduction block compared to those with intact Purkinje activation during NS-LBBP (181 ms [IQR: 162-195 ms] vs 157 ms [IQR: 139-168 ms]; P = 0.022). CONCLUSIONS: In contrast to His-bundle pacing, S-LBBP predominantly yields a wide QRS as a result of delayed RBB synchronization, whereas NS-LBBP results in shorter QRS duration because of recruitment of the basal right ventricular septum. A wider-paced morphology of LBBP was noted in patients with complete conduction block caused by bidirectional left intrahisian block. Achievement of narrow QRS during LBBP is predicated upon capture nonselectivity or programmed atrioventricular fusion, rather than intrinsic physiologic synchrony from left bundle branch stimulation.

Knockdown of TRIM65 suppressed the proliferation and invasiveness of gastric cancer cells by restricting the ubiquitin degradation of PPM1A.

Gastric cancer is a type of serious malignant tumors all around the world. TCGA data showed that the expression of TRIM65 (E3 ubiquitin ligase) was enhanced in the gastric cancer tissues. The role of TRIM65 in the tumorigenesis of gastric cancer remains unclear. In this study, we successfully established TRIM65-knockdown gastric cancer cells. Next, CCK-8, colony formation assays and transwell assays were performed to detect the cell proliferation and invasion. The results showed that suppression of TRIM65 inhibited the proliferation and invasion of gastric cancer cells. Interestingly, the Western blot assay confirmed that downregulation of TRIM65 increased the level of PPM1A and decreased the level of p-TBK1 in gastric cancer cells. Mechanistically, immunoprecipitation assay revealed that knockdown of TRIM65 inhibited the ubiquitin degradation of PPM1A. In rescue experiments, suppression of PPM1A promoted the proliferation and invasion of gastric cancer cells transfected with sh-TRIM65. Therefore, our results suggested that knockdown of TRIM65 inhibited the proliferation and invasion of gastric cancer cells by suppressing the ubiquitin degradation of PPM1A and phosphorylation of TBK1.