Inflammation plays a vital role in the occurrence and progression of atrial fibrillation (AF). The association between pericoronary adipose tissue attenuation (PCATA) and AF recurrence following ...ablation has not been fully clarified.
We aimed to evaluate the association between PCATA and AF recurrence after radiofrequency catheter ablation (RFCA).
Patients who underwent the first RFCA for AF and performed coronary computed tomography angiography before ablation between 2018 and 2021 were enrolled. The predictive values of PCATA for AF recurrence after ablation were investigated. The area under curve (AUC), relative integrated discrimination improvement (IDI), and categorical free net reclassification improvement (NRI) were used to assess the discrimination ability of different models for AF recurrence.
During 1-year follow-up, 34.1% patients experienced AF recurrence. The multivariable analysis model revealed that PCATA of the right coronary artery (RCA) was an independent risk factor for AF recurrence. Patients with a high level of RCA-PCATA had a high risk of recurrence, after adjusting for other risk factors by restricted cubic splines. The performance in predicting AF recurrence was significantly improved by adding the marker of RCA-PCATA to the clinical model (AUC: 0.724 vs. 0.686, p = .024), with a relative IDI of 0.043 (p = .006) and continuous NRI of 0.521 (p < .001).
PCATA of RCA was independently associated with AF recurrence after ablation. PCATA may be helpful for risk classification for AF ablation patients.
This paper numerically investigated the dynamic characteristics of combustion in a model scramjet. Three-dimensional compressible large eddy simulation was performed on a hydrogen fueled combustor ...and pressure fluctuations were recorded. The analysis of pressure data showed that the combustion processes are intrinsically unstable under supersonic air inflow conditions. Flame dynamics were convinced by the fluctuations in flame lift-off distance away from the strut base. Combined with the corresponding time interval, instantaneous flame speed was calculated. Results indicated that pressure oscillations at different locations show difference in amplitude, frequency, and the underlying control mechanism. Flame front oscillation analysis showed that the flame–shock interaction in the strut recirculation zone was responsible for the combustion instability. Flame dynamics were compared with low-speed turbulent lifted flames. The transition between flame propagation just after the strut and shock-induced combustion in the subsonic bubble at the intersection of two wall-reflected oblique shocks made for the flame stabilization.
•The reasons for pressure oscillation at different locations are distinguished.•Flame lift-off distance and the instantaneous flame speed are quantified.•Intermittent formation of subsonic bubble controls the combustion oscillation.•Flame propagation and shock-induced combustion jointly stabilize the flame.
Previous studies have revealed significant differences in microbiome compositions between infants delivered via cesarean section (C-section) and natural vaginal birth. However, the importance of the ...delivery mode in the first days of life remains unclear. Importantly, this stage is minimally affected by infant feeding. Here, we used a metagenomic sequencing technique to characterize the meconium microbiome from the feces of a Chinese cohort of vaginally and C-section-delivered infants, including in vitro fertilization (IVF) newborns, during the first 24 h after birth. Meconium microbiome diversity was higher in vaginally delivered infants than that in C-section-delivered infants. Propionibacterium species were most abundant in the vaginally delivered infants, whereas the C-section group had high levels of Bacillus licheniformis. The two IVF newborns delivered by C-section harbored microbial communities similar to the vaginal microbiome in terms of taxonomic composition. Metabolic functions of the C-section group suffered more from the influence of the dominant group (B. licheniformis), whereas the vaginal group was more homogeneous, with a metabolism dominated by multi-microbes. Moreover, different modes of delivery affected the antibiotic resistance gene (ARG) prevalence. These findings provide novel information for the development of strategies to guide a healthy mode of delivery and promote the formation of healthy microbiota.
Autophagy and the ubiquitin proteasome system (UPS) are two major protein degradation pathways involved in brain ischemia. Autophagy can compensate for UPS impairment‑induced cellular dysfunction. ...HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1 (Huwe1), an E3 ubiquitin ligase, serves critical roles in nervous system plasticity, regeneration and disease. However, the role of Huwe1 in autophagy in brain ischemia/reperfusion (I/R) injury remains unknown. The aim of the present study was to investigate the crosstalk between autophagy and the UPS in brain ischemia. The present study established an oxygen‑glucose deprivation and reperfusion (OGD/R) model in rat primary cortex neurons in vitro. Lentiviral interference was used to silence the expression of Huwe1. An autophagy promoter (rapamycin), an autophagy inhibitor (wortmannin) and a JNK pathway inhibitor (SP600125) were also used in the current study. Cellular autophagy‑related proteins, including Beclin‑1, autophagy related (ATG) 7, ATG5, ATG3 and microtubule associated protein 1 light chain 3 α, and apoptosis‑related proteins, such as P53, cleaved caspase 3, Bax and Bcl2, were detected via western blotting and immunocytochemistry. Neuronal apoptosis was evaluated using a TUNEL assay. The results demonstrated that silencing Huwe1 increased the expression levels of autophagy‑related proteins at 24 h after OGD/R. Treatment with a JNK inhibitor or cotreatment with Huwe1 shRNA significantly increased autophagy. Rapamycin increased apoptosis under OGD/R conditions. However, treatment with Huwe1 shRNA decreased the number of TUNEL‑positive cells at 24 h after OGD/R. Cotreatment with Huwe1 shRNA and wortmannin alleviated neuronal apoptosis under OGD/R conditions compared with cotreatment with DMSO. Collectively, the present results suggested that silencing Huwe1 was accompanied by a compensatory induction of autophagy under OGD/R conditions. Furthermore, the JNK pathway may be a key mediator of the interaction between Huwe1 and autophagy in response to UPS impairment.
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) monotherapy is the standard of care in treating advanced non-small cell lung cancer (NSCLC). Nevertheless, whether adding ...pemetrexed-based chemotherapy to EGFR-TKI targeted therapy furtherly prolongs survival outcomes and improves responses remains controversial. Therefore, we conducted this pooled analysis to compare the efficacy and tolerability between gefitinib plus pemetrexed-based chemotherapy and gefitinib alone in the first-line treatment of advanced NSCLC patients with mutated EGFR. We systematically searched PubMed, Web of Science, Embase, and Cochrane CENTRAL on June 23, 2022. Eligible studies were registered randomized clinical trials comparing gefitinib plus pemetrexed-based chemotherapy with gefitinib alone. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Objective response rate (ORR), disease control rate (DCR), and discontinuation rate (DR) were explored as secondary outcomes. Eight studies within five randomized clinical trials were eligible. Gefitinib combined with pemetrexed-based chemotherapy significantly prolonged OS (hazard ratio HR 0.57, 95% confidence interval CI 0.37-0.89, p = 0.0125) and PFS (HR 0.52, 95% CI 0.39-0.70, p < 0.0001) versus gefitinib alone. In subgroup analysis, patients with EGFR exon 19 deletion and exon 21 L858R could benefit from the addition of pemetrexed-based chemotherapy to gefitinib in terms of PFS (EGFR exon 19 deletion: HR 0.50, 95% CI 0.34-0.75, p = 0.0008; EGFR exon 21 L858R: HR 0.46, 95% CI 0.26-0.82, p = 0.0079) but not OS. In addition, ORR was improved after the administration of gefitinib plus pemetrexed-based chemotherapy against gefitinib (odds ratio OR 1.91, 95% CI 1.44-2.55, p < 0.0001). Both strategies showed comparable DCRs (OR 1.46, 95% CI 0.94-2.26, p = 0.0952) and DRs (risk ratio RR 2.80, 95% CI 0.69-11.44, p = 0.1509). Compared with gefitinib alone, combining pemetrexed-based chemotherapy with gefitinib significantly improved OS and PFS in advanced EGFR-mutant NSCLC patients with acceptable tolerability. However, the accurate sub-population who could have OS benefits requires further validation.
DDX41 is an intracellular DNA sensor that evokes type I interferon (IFN-I) production via the adaptor stimulator of interferon gene (STING), triggering innate immune responses against viral ...infection. However, the regulatory mechanism of the DDX41-STING pathway in teleost fish remains unclear. The mandarin fish (
) is a cultured freshwater fish species that is popular in China because of its high market value. With the development of a high-density cultural mode in mandarin fish, viral diseases have increased and seriously restricted the development of aquaculture, such as ranavirus and rhabdovirus. Herein, the role of mandarin fish DDX41 (
DDX41) and its DEAD and HELIC domains in the antiviral innate immune response were investigated. The level of
DDX41 expression was up-regulated following treatment with poly(dA:dT) or Mandarin fish ranavirus (MRV), suggesting that
DDX41 might be involved in fish innate immunity. The overexpression of
DDX41 significantly increased the expression levels of IFN-I, ISGs, and pro-inflammatory cytokine genes. Co-immunoprecipitation and pull-down assays showed that the DEAD domain of
DDX41 recognized the IFN stimulatory DNA and interacted with STING to activate IFN-I signaling pathway. Interestingly, the HELIC domain of
DDX41 could directly interact with the N-terminal of STING to induce the expression levels of
and
genes. Furthermore, the
DDX41 could enhance the
STING-induced IFN-I immune response and significantly inhibit MRV replication. Our work would be beneficial to understand the roles of teleost fish DDX41 in the antiviral innate immune response.
Tailoring the combustion performance of propellant plays an important role in solid propellant design. Herein, we present that interfacial reaction (thermite reaction on Al surface) could be used for ...tuning the combustion performance of Al-based propellants. Two interfacial reactions included Al-based core-shell composites Al@PDA@CuO (Al@CuO) and Al@PDA@PVDF (Al@PVDF) were prepared and characterized. It is found that both Al@CuO and Al@PVDF have slightly decreased heat release and density, but significantly promote Al combustion, in comparison to the mechanically mixed ones without interfacial reaction. Experiments on ignition, combustion, agglomeration, and thermal property of those propellants containing core-shell Al-based composites have been carried out. The results show that both Al-CuO and Al-PVDF interfacial reactions could reduce the ignition delay time and improve the burn rate of propellant due to the low initial reaction temperature and generated high heat. In addition, it is also found that the interfacial reaction between Al and CuO could increase the size of condensed combustion products of the propellants due to the formation of AlCu4. However, average condensed combustion product diameter of the propellant using Al@PVDF as the fuel is 0.47 µm, which is smaller than that of propellant using mechanically mixed Al/PVDF as the fuel (0.61 µm). This is a 23% decrease in agglomerate diameter compared with agglomerates formed from the propellant without interfacial reaction. These results reveal that different interfacial reaction may result in very different oxidation reaction mechanisms of Al that controls the combustion performances of the Al-based propellants.
gem‐Difluoropropargyl bromides are versatile intermediates in organic synthesis, but have rarely been employed in transition‐metal‐catalyzed cross‐coupling reactions. The first palladium‐catalyzed ...gem‐difluoropropargylation of organoboron reagents with gem‐difluoropropargyl bromides is now reported. The reaction proceeds under mild reaction conditions with high regioselectivity; it features a broad substrate scope and excellent functional‐group compatibility and thus provides an attractive approach for the synthesis of complex fluorinated molecules, in particular for drug discovery and development.
gem‐Difluoropropargylation: A palladium‐catalyzed gem‐difluoropropargylation of aryl and alkenyl boronic acids and boronates with gem‐difluoropropargyl bromides has been developed (see Scheme). This cross‐coupling process represents an attractive approach for the synthesis of complex fluorinated molecules, in particular for drug discovery and development.
Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD). Deubiquitinase cylindromatosis (CYLD) has been reported to significantly aggravate vascular smooth ...muscle cell (VSMC) phenotypic transformation, proliferation, and migration. Here, we aimed to further investigate its roles and underlying mechanisms in the CHD‐PAH development. The expression of CYLD in the lung tissues from CHD‐PAH patients and monocrotaline (MCT) plus aortocaval (AV)‐induced PAH rats, pulmonary artery smooth muscle cells (PASMCs) from MCT‐AV‐induced PAH rats, and human PASMCs (HPASMCs) was evaluated. After infection with CYLD siRNA or pcNDA3.1‐CYLD, the proliferation, migration, and apoptosis of HPASMCs were measured using an EdU assay, transwell and scratch wound healing assays, and flow cytometric assay, respectively. An adeno‐associated virus (AAV) vector encoding CYLD was used to suppress CYLD expression by being intratracheally instilled in rats 7 days before MCT‐AV treatment. The results showed that CYLD was increased in the lung tissues from CHD‐PAH patients and MCT‐AV‐induced PAH rats, and in PASMCs from MCT‐AV‐induced PAH rats. The contractile‐type HPASMCs expressed low levels of CYLD, while the proliferative synthetic‐type HPASMCs expressed high levels of CYLD. In addition, CYLD could mediate HPASMC dysfunction, which regulated HPASMC phenotypic transformation and proliferation via the modulation of p38 and ERK activation, while CYLD regulated HPASMC migration via the modulation of p38 activation. In vivo results demonstrated that the local suppression of CYLD expression could attenuate the increased levels of PAH and its associated pulmonary vascular remodeling in MCT‐AV‐induced PAH rats. Collectively, these results indicated that CYLD might be a potential novel therapeutic target for the prevention of PAH and pulmonary vascular remodeling in CHD‐PAH through the modulation of HPASMC dysfunction.
CYLD might be a potential novel therapeutic target for the prevention of PAH and pulmonary vascular remodeling in CHD‐PAH through the modulation of HPASMC dysfunction.
Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present ...before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens.
Diagnosis and treatment of Hu-PNS.
This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination.
The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy.
The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence.
Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.
PDF
