Assess the Outcomes of Transcatheter Aortic Valve Replacement in Bicuspid Valve with Mixed Disease versus Predominant Aortic Stenosis.

Purpose: In mixed aortic valve disease (MAVD), the results of transcatheter aortic valve replacement (TAVR) are conflicting. There is limited data on the outcomes of TAVR in patients with bicuspid aortic valve (BAV) and MAVD. The objective of this study is to compare outcomes after TAVR in BAV patients with MAVD and predominant aortic stenosis (PAS). Patients and Methods: Patients with BAV who underwent TAVR between January 2016 and April 2023 were included. The primary outcome was device success. The secondary endpoints were periprocedural mortality and other complications as defined by the Valve Academic Research Consortium-3 (VARC-3). Propensity score matching was used to minimize potential confounding. Results: A total of 262 patients were included in this study, 83 of whom had MAVD. The median age was 72 years, and 55.7% were male. The baseline comorbidity risk files were comparable between the two groups. Patients with MAVD had more mitral regurgitation, tricuspid regurgitation and pulmonary hypertension, larger annular and left ventricular outflow tract dimensions, and more severe calcification than PAS. In the unmatched population, MAVD patients had similar device success rate (69.9% vs 79.9%, P=0.075) and 30-day mortality (3.6% vs 3.4%, P=1) compared to PAS. Propensity score matching resulted in 66 patient pairs. Device success rate were still comparable in the matched population. Other clinical outcomes, including stroke, bleeding (type 2-4), major vascular complications, acute kidney injury (stage 2-4) and permanent pacemaker implantation, were comparable between the two groups. Multivariable logistic regression analysis did not show MAVD to be an independent negative predictor of device success. At one year, survival was similar between patients with MAVD and those with PAS. Conclusion: For the bicuspid valve, patients with MAVD had a more challenging anatomy. MAVD patients associated with comparable 30-day clinical outcomes after TAVR compared to PAS patients in patients with BAV.

Incidence, Predictors, and Implications of Secondary Aortic Intervention Following Thoracic Endovascular Aortic Repair for Type B Dissection.

BACKGROUND: Secondary aortic intervention (SAI) following thoracic endovascular aortic repair (TEVAR) is not uncommon. However, a satisfactory management system has not been established for these patients. We aimed to report our single-center experience with SAI after prior TEVAR for type B aortic dissection (TBAD). METHODS: From January 2010 to May 2017, 860 eligible patients with TBAD underwent TEVAR. One hundred seven (12.4%) patients required SAI, either endovascularly (n=76) or surgically (n=31). The main indications for SAI were entry flow (n=58 [54.2%]), aneurysm expansion of the proximal or remote aorta (n=26 [24.3%]), retrograde type A aortic dissection (n=11 [10.3%]), distal stent-graft-induced new entry tear (n=6 [5.6%]), and stent migration (n=4 [3.7%]). The Kaplan-Meier curves were generated to determine the degree of freedom from SAI and the prognosis. Cox proportional hazards were used to screen for risk factors for SAI and poor prognosis. RESULTS: The overall 30-day mortality rate after SAI was 4.7% (n=5): endovascular (n=2 [2.6%]) vs open surgery (n=3 [9.7%]; p=0.145). The cumulative survival rates with or without SAI were 86.3%±3.6% vs 95.7%±0.8% at 3 years and 82.0%±4.2% vs 92.2%±1.1% at 5 years, respectively (log-rank p<0.001). Although no significant difference in survival was observed, the incidence of SAI was significantly greater in patients who underwent TEVAR during the chronic phase (acute [11.6%] vs subacute [9.6%] vs chronic [27.8]; p<0.001). Multivariate regression analysis revealed that prior TEVAR in the chronic phase (hazard ratio [HR]=1.73, 95% confidence interval [CI]=1.03-2.90; p=0.039), maximum aortic diameter (HR=1.05, 95% CI=1.04-1.07; p<0.001), and arch involvement (HR=1.48, 95% CI=1.01-2.18; p=0.048) were predictors of the incidence of SAI. In addition, the maximum aortic diameter was demonstrated to be the only risk factor for prognosis after adjusting for confounding factors. CONCLUSIONS: Thoracic endovascular aortic repair for chronic TBAD patients should be reconsidered. Open surgery is preferable for those with proximal progression, whereas endovascular treatment is more suitable for distal lesions. Close surveillance and timely reintervention after TEVAR, whether via endovascular techniques or open surgery, are necessary to prevent devastating complications. CLINICAL IMPACT: The management of patients with type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR) is challenging. We summarized our single-center experience regarding secondary aortic intervention after TEVAR for TBAD. We found that TEVAR for chronic TBAD patients should be carefully evaulated, and open surgery is recommended for those with proximal progession, while endovascular treatment is more preferable for distal lesions.

The causal relationship between metabolic syndrome and its components and cardiovascular disease: A mendelian randomization study.

AIM: To investigate the causal relationship between metabolic syndrome (MetS) and its components and 14 cardiovascular diseases using Mendelian randomization (MR). METHODS: We used summary statistics from large-scale genome-wide association studies of MetS, its components, and cardiovascular diseases. We performed a two-sample MR analysis using the inverse-variance weighted method and other sensitivity methods. We also performed multivariate MR to adjust for potential risk factors. RESULTS: Our study found that MetS was causally associated with an increased risk of ischemic stroke, abdominal aortic aneurysm, pulmonary embolism, coronary heart disease, heart failure, and peripheral artery disease. Waist circumference was causally associated with an increased risk of 6 cardiovascular diseases. Type 2 diabetes mellitus, diastolic blood pressure, systolic blood pressure, triglycerides, and high-density lipoprotein cholesterol were all causally associated with coronary heart disease, with varying causal relationships with the remaining 5 cardiovascular diseases. Multivariate MR showed that, except for ischaemic stroke, waist circumference remained causally associated with the remaining five cardiovascular diseases after adjusting for potential confounders. CONCLUSION: Our study provides evidence that metabolic syndrome is causally associated with 6 cardiovascular diseases. Waist circumference is the most important component of these relationships. These findings have implications for the prevention and management of metabolic syndrome and cardiovascular diseases.

Piperine improves levodopa availability in the 6-OHDA-lesioned rat model of Parkinson's disease by suppressing gut bacterial tyrosine decarboxylase.

AIM: Tyrosine decarboxylase (TDC) presented in the gut-associated strain Enterococcus faecalis can convert levodopa (L-dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L-dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria-mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L-dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L-dopa on Parkinson's disease (PD). METHODS: Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis. Then, the inhibitory effects of PIP on L-dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L-dopa and PIP on 6-hydroxydopamine (6-OHDA)-lesioned rats and tested the regulations of L-dopa bioavailability and brain DA level by pharmacokinetics study and MALDI-MS imaging. Finally, we evaluated the microbiota-dependent improvement effect of PIP on L-dopa availability using pseudo-germ-free and E. faecalis-transplanted rats. RESULTS: We found that PIP combined with L-dopa could better ameliorate the move disorders of 6-OHDA-lesioned rats by remarkably improving L-dopa availability and brain DA level than L-dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L-dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6-OHDA-lesioned rats. CONCLUSION: Oral administration of L-dopa combined with PIP can improve L-dopa availability and brain DA level in 6-OHDA-lesioned rats by suppressing intestinal bacterial TDC.

Piperine promotes PI3K/AKT/mTOR-mediated gut-brain autophagy to degrade α-Synuclein in Parkinson's disease rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum L., a medicinal and food homologous herb, has a traditional history of use in treating gastrointestinal and neurological disorders. Piperine (PIP) the main alkaloid of P. longum, exists neuroprotective effects on various animal models of Parkinson's disease (PD). Nevertheless, the underlying mechanism, particularly the role of PIP in promoting gut-brain autophagy for α-Synuclein (α-Syn) degradation in PD, remains incompletely understood. AIM OF THE STUDY: To explore the role of PIP in regulating the gut-brain autophagy signaling pathway to reduce α-Syn levels in both the colon and substantia nigra (SN) of PD model rats. MATERIALS AND METHODS: Behavioral experiments were conducted to assess the impact of PIP on 6-hydroxydopamine (6-OHDA)-induced PD rats. The intestinal microbiome composition and intestinal metabolites were analyzed by metagenomics and GC-MS/MS. The auto-phagosomes were visualized by transmission electron microscopy. Immunohistochemistry, immunofluorescence, and western blotting were performed to assess the levels of tyrosine hydroxylase (TH), α-Syn, LC3II/LC3I, p62, and the PI3K/AKT/mTOR pathway in both the SN and colon of the rats. The pathway-related inhibitor and agonist were used to verify the autophagy mechanism in the SH-SY5Y cells overexpressing A53T mutant α-Syn (A53T-α-Syn). RESULTS: PIP improved autonomic movement and gastrointestinal dysfunctions, reduced α-Syn aggregation and attenuated the loss of dopaminergic neurons in 6-OHDA-induced PD rats. After oral administration of PIP, the radio of LC3II/LC3I increased and the expression of p62 was degraded, as well as the phosphorylation levels of PI3K, AKT and mTOR decreased in the SN and colon of rats. The effect of PIP on reducing A53T-α-Syn through the activation of the PI3K/AKT/mTOR-mediated autophagy pathway was further confirmed in A53T-α-Syn transgenic SH-SY5Y cells. This effect could be inhibited by the autophagy inhibitor bafilomycin A1 and the PI3K agonist 740 Y-P. CONCLUSIONS: Our findings suggested that PIP could protect neurons by activating autophagy to degrade α-Syn in the SN and colon, which were related to the suppression of PIP on the activation of PI3K/AKT/mTOR signaling pathway.

Hybrid Technique Outcomes for High-Risk Uncomplicated Type B Aortic Dissection With Landing Zone 1.

In this report, we analyzed the outcomes of the hybrid technique for high-risk uncomplicated type B aortic dissection with landing zone 1. We enrolled 80 patients from January 2016 to January 2020 and retrospectively analyzed their outcomes, including mortality, aortic-related adverse events, and aortic remodeling. The mean age was 51.6 ± 9.9 years, and 68.0% (54 of 80) were men. Technical success was achieved in 100% of cases (80 of 80), and 30-day mortality was 4% of patients (n = 3), including 2 dissection-related deaths. Immediate endoleaks occurred in 16 patients, including 11 type Ia and 5 type II. Four patients (5%) developed minor strokes postoperatively, and no short-term spinal cord ischemia and re-intervention occurred. The average length of stay was 20 ± 8 days. The overall mortality was 8% after a median follow-up of 44 months (38 to 52). Five patients (7%) developed strokes, and 11 (16%) had late endoleaks, including 1 type Ia, 5 type Ib, and 3 type II. Four re-interventions (5%) were necessary, 3 for endoleaks and 1 for retrograde type A dissection. Three bypass graft occlusions (5%) and 5 stoma stenoses (8%) were observed in the latest follow-up computed tomography. In conclusion, the hybrid technique with landing zone 1 might be a viable alternative to open aortic arch replacement in patients at high risk with uncomplicated type B aortic dissection with acceptable early and late outcomes. However, stroke and endoleak complications should be further addressed.

[Review of traditional Chinese medicines in ameliorating neuropsychiatric diseases by improving the levels of monoamine neurotransmitters via gut microbiota regulation].

The degeneration of monoaminergic system and the reduction of monoamine neurotransmitters(MNTs) are associated with the occurrence of a variety of neuropsychiatric diseases, becoming the key indicators for clinical diagnosis and treatment. Recent studies suggested gut microbiota could influence the occurrence, development, and treatment of neuropsychiatric diseases by directly or indirectly regulating the synthesis and metabolism of MNTs. Rich clinical experience has been accumulated in the amelioration and treatment of neuropsychiatric diseases by traditional Chinese medicines. The traditional oral administration method demonstrates obvious advantages in regulating gut microbiota. It provides a new idea for explaining the pharmacodynamic material basis and mechanism of traditional Chinese medicines in ameliorating neuropsychiatric disease by improving the levels of MNTs via gut microbiota regulation. Focusing on three common neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, and major depression, we summarized the pathways of gut microbiota in regulating the levels of MNTs and the paradigms of traditional Chinese medicines in ameliorating neuropsychiatric diseases via the "bacteria-gut-brain axis", aiming to provide ideas for the development of drugs and treatment schemes.

Effects of combining multiple dose reduction techniques on coronary computed tomography angiography.

BACKGROUND: Coronary computed tomography angiography (CCTA) is the preferred non-invasive examination method for coronary heart disease. However, the radiation from computed tomography has become a concern since public awareness of radiation hazards continue to increase. AIM: To explore the value of multiple dose reduction techniques for CCTA. METHODS: Consecutive normal and overweight patients were prospectively divided into two groups: Group A1, patients who received multiple dose reduction scans (n = 82); and group A2, patients who received conventional scans (n = 39). The scan parameters for group A1 were as follows: Isocentric scan, tube voltage = 80 kV, and tube current control using 80% smart milliampere. The scan parameters for group A2 were as follows: Normal position, tube voltage = 100 kV, and smart milliampere. RESULTS: The average effective doses (EDs) for groups A1 and A2 were 1.13 ± 0.35 and 3.36 ± 1.30 mSv, respectively. There was a statistically significant difference in ED between the two groups (P < 0.01). Furthermore, noise was significantly lower, and both signal-to-noise ratio and contrast signal-to-noise ratio were higher in group A2 when compared to group A1 (P < 0.01). Moreover, the subjective image quality (IQ) scores were excellent in both groups, in which there was no significant difference in subjective IQ score between the two groups (P = 0.12). CONCLUSION: Multiple dose reduction scan techniques can significantly decrease the ED of patients receiving CCTA examinations for clinical diagnosis.

Reconfigurable terahertz light harvesting with MoTe2 hybrid metasurface.

Near-perfect light harvesting of a metasurface-based absorber paves the way for achieving numerous potential applications in sensing, cloaking, and photovoltaics. Here, we present a reconfigurable perfect absorber based on a molybdenum ditelluride (MoTe2) hybrid metasurface at terahertz (THz) frequency. By investigating the optical response of metasurface-based absorbers, a reconfigurable switching of dual-frequency perfect absorption to a new single-frequency absorption takes place when light illuminates MoTe2. Moreover, the absorption mechanism of the hybrid metasurface is well demonstrated with the analytical coupled-dipole model and impedance analysis. The proposed reconfigurable THz meta-absorber provides a new, to the best of our knowledge, route for active radar stealth, frequency-selective detection, and next-generation wireless communication.

Re-evaluate the Prognostic Value of Absolute Lymphocyte Count in Pediatric Immune Thrombocytopenia.

To re-evaluate the prognostic value of absolute lymphocyte count (ALC) in pediatric immune thrombocytopenia (ITP) from the perspective of age. A total of 242 ITP pediatric patients, including 141 newly diagnosed ITP (nITP), 89 chronic ITP (cITP), and 12 persistent ITP, were retrospectively reviewed for this study. These patients were divided into 3 groups according to age (group 1, ≤24 m; group 2, 24-72 m; and group 3, >72 m). The ALC detected at admission was significantly different between nITP and cITP patients without considering their age difference (5.22 vs. 3.55×10 9 /L, P <0.001). However, no significant difference was discovered after age stratification (≤24 m: 6.52 vs. 5.34×10 9 /L, P =0.161; 24-72 m: 3.78 vs. 3.63×10 9 /L, P =0.748; > 72 m: 2.53 vs. 2.40×10 9 /L, P =0.748). ROC analysis showed that the prognostic value of ALC in ITP children was limited (area under curve (AUC): ≤24 m, 24-72 m, and >72 m were 0.591, 0.570, and 0.542, respectively). Analysis of covariance showed there was no significant difference in ALC between nITP and cITP when considering age as a covariate ( P =0.131). Instead, the ROC showing that platelet to lymphocyte ratio (PLR) has prognostic value in pediatric ITP independent of age stratification (≤24 m: AUC, 0.688; 24-72 m: AUC, 0.741; >72 m: AUC, 0.680). In conclusion, there was no significant difference of ALC between nITP and cITP patients when stratified by different age groups, and PLR may be an optional prognostic indicator for ITP.

The impact of machine-learning-derived lean psoas muscle area on prognosis of type B aortic dissection patients undergoing endovascular treatment.

OBJECTIVES: The aim of this work was to investigate the impact of machine-learning-derived baseline lean psoas muscle area (LPMA) for patients undergoing thoracic endovascular aortic repair. METHODS: A retrospective study was undertaken of acute and subacute complicated type B aortic dissection patients who underwent endovascular treatment from 2010 to 2017. LPMA (a marker of frailty) was calculated by multiplying psoas muscle area and density measured at L3 level from the computed tomography. The optimal cut-off value of LPMA was determined by the Cox hazard model with restricted cubic spline. RESULTS: A total of 428 patients who met the inclusion criteria were included in this study. Patients were classified into low LPMA group (n = 218) and high LPMA group (n = 210) using the cut-off value of 395 cm2 Hounsfield unit. An automatic muscle segmentation algorithm was developed based on U-Net architecture. There was high correlation between machine-learning method and manual measurement for psoas muscle area (r = 0.91, P < 0.001) and density (r = 0.90, P < 0.001). Multivariable regression analyses revealed that baseline low LPMA (<395 cm2 Hounsfield unit) was an independent positive predictor for 30-day (odds ratio 5.62, 95% confidence interval 1.20-26.23, P = 0.028) and follow-up (hazard ratio 5.62, 95% confidence interval 2.68-11.79, P < 0.001) mortality. Propensity score matching and subgroup analysis based on age (<65 vs ≥65 years) confirmed the independent association between baseline LPMA and follow-up mortality. CONCLUSIONS: Baseline LPMA could profoundly affect the prognosis of patients undergoing thoracic endovascular aortic repair. It was feasible to integrate the automatic muscle measurements into clinical routine.

Penthorum chinense Pursh. extract attenuates non-alcholic fatty liver disease by regulating gut microbiota and bile acid metabolism in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Penthorum chinense Pursh. (PCP) is commonly used as a Miao ethnomedicine and health food for liver protection in China. Gansukeli (WS3-B-2526-97) is made from the extract of PCP (PCPE) for the treatment of viral hepatitis. In recent years, PCPE has been reported in the treatment of non-alcoholic fatty liver disease (NAFLD), however its potential mechanism is not fully elucidated. AIM OF THE STUDY: To investigate the ameliorating effect of PCPE on high-fat diet (HFD)-induced NAFLD mice and demonstrate whether its protective effect is gut microbiota dependent and associated with bile acid (BA) metabolism. MATERIALS AND METHODS: The alleviating effect of PCPE on NAFLD was conducted on male C57BL/6J mice fed an HFD for 16 weeks, and this effect associated with gut microbiota dependent was demonstrated by pseudo-germfree mice treated with antibiotics and fecal microbiota transplantation (FMT). The composition of the gut microbiota in the cecum contents was analyzed by 16S rRNA sequencing, and the levels of BAs in liver and fecal samples were determined by UPLC/MS-MS. RESULTS: The results showed that administration of PCPE for 8 weeks could potently ameliorate HFD-induced NAFLD and alleviate dyslipidemia and insulin resistance. Moreover, PCPE treatment alleviated gut dysbiosis, especially reducing the relative abundance of bile salt hydrolase (BSH)-producing bacteria. Furthermore, PCPE significantly increased the levels of taurine-conjugated BAs in feces, such as tauro-ß-muricholic acid (T-ßMCA), tauroursodesoxycholic acid (TUDCA), and taurochenodeoxycholic acid (TCDCA), and increased hepatic chenodeoxycholic acid (CDCA). The protein and mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were decreased in intestine, increased taurine-conjugated BAs inhibited the intestinal signaling pathway, which was associated with increased genes expression of enzymes in the alternative BA synthesis pathway that reduced the levels of cholesterol. The increased CDCA produced via the alternative BA synthesis pathway promoted hepatic FXR activation and BA excretion. CONCLUSION: Our study is the first time to demonstrate that PCPE could ameliorate NAFLD in HFD-induced mice by regulating the gut microbiota and BA metabolism, and from a novel perspective, to clarify the mechanism of PCPE in NAFLD.

Dihydroflavonoids as Bioactive Components of Penthorum chinense, a Miao Ethnomedicine, against NAFLD through Bile Acid Metabolism Pathway.

Penthorum chinense Pursh. is a traditional herbal medicine of Miao, and its extracts (PCPE) have been used for treatment of liver diseases in the clinic including nonalcoholic fatty liver disease (NAFLD). However, the active components and pharmacological mechanisms of PCPE for treating NAFLD remain unclear. This study aimed to explore potential mechanisms of action through network pharmacology, molecular docking combined with experimental in vitro. A total of five dihydroflavonoids (1-5) with the same parent nucleus of pinocembrin (PCB) from PCPE, were selected as bioactive ingredients and 109 potential targets related to NAFLD were obtained from public databases and literature mining. The core targets related to the bile secretion signaling were selected based on PPI network and KEGG enrichment analysis for exploring the mechanism of PCPE against NAFLD. Molecular docking results showed good interaction between the core targets in bile secretion signaling pathway and the five compounds predicted to be bioactive. With the strong binding activity to retinoid X receptor-alpha (RXRA) and farnesoid X receptor (FXR) protein, pinocembrin-7-O-ß-D-glucoside (PCBG, the highest content in PCPE) and its metabolite PCB, could significantly increase the expression of RXRA, FXR and bile salt export pump (BSEP) in L02 cells, and significantly decrease the expression of cholesterol 7α-hydroxylase (CYP7A1) at mRNA and protein levels. This study provided favorable evidence for mechanism of the main dihydroflavonoids of PCPE against NAFLD, and presented a paradigm for the study of ethnomedicine.

RING-Finger Protein 6 promotes Drug Resistance in Retinoblastoma via JAK2/STAT3 Signaling Pathway.

Chemotherapy is the first-line treatment for human retinoblastoma (RB), but the occurrence of drug resistance greatly limited its efficacy in practice. RING-finger protein 6 (RNF6) is an E3 ubiquitin ligase that is aberrantly upregulated in a range of cancers and plays important roles in cancer progression. However, the role of RNF6 in RB is largely unknown. In this study, we investigated the role of RNF6 in RB drug resistance. Two carboplatin-resistant RB cells, Y-79/CR and SO-Rb50/CR, were generated based on Y-79 and SO-Rb50 cells. RT-PCR and western blot analyses showed that RNF6 expression on both mRNA and protein levels was significantly increased in Y-79/CR and SO-Rb50/CR cells comparing to their parental cells. Knockdown of RNF6 using siRNA in Y-79/CR and SO-Rb50/CR cells resulted in cells sensitive to carboplatin on a RNF6 siRNA dose dependent manner. Similarly, RNF6 overexpression in parental Y-79 and SO-Rb50 cells could help cells gain resistance to carboplatin on a RNF6 expression dependent manner. Signaling pathway analyses revealed that JAK2/STAT3 pathway was involved in the RNF6-induced carboplatin resistance in RB cells. We further revealed that RNF6 expression in both Y-79 and SO-Rb50 cells could render cells resistant to multiple anti-cancer drugs including carboplatin, vincristine and etoposide, an implication of RNF6 as a biomarker for RB drug resistance. Taken together, our study has revealed that RNF6 is upregulated in drug-resistant RB cells and RNF6 promotes drug resistance through JAK2/STAT3 signaling pathway. The importance of RNF6 in RB cells drug resistance may represent this protein as a potential biomarker and treatment target for drug resistance in RB.

Coronary artery disease as an independent predictor of short-term and long-term outcomes in patients with type-B aortic dissection undergoing thoracic endovascular repair.

Background and aims: Previous studies reported a high prevalence of concomitant coronary artery disease (CAD) in patients with Type B aortic dissection (TBAD). However, there is too limited data on the impact of CAD on prognosis in patients with TBAD. The present study aimed to assess the short-term and long-term impact of CAD on patients with acute or subacute TBAD undergoing thoracic endovascular aortic repair (TEVAR). Methods: We retrospectively evaluated 463 patients with acute or subacute TBAD undergoing TEVAR from a prospectively maintained database from 2010 to 2017. CAD was defined before TEVAR by coronary angiography. Multivariable logistic and cox regression analyses were performed to evaluate the relationship between CAD and the short-term as well as long-term outcomes. Results: According to the results of coronary angiography, the 463 patients were divided into the following two groups: CAD group (N = 148), non-CAD group (N = 315). In total, 12 (2.6%) in-hospital deaths and 54 (12%) all-cause deaths following a median follow-up of 48.1 months were recorded. Multivariable analysis revealed that CAD was an independent predictor of in-hospital major adverse clinical events (MACE) (odd ratio [OR], 2.33; 95% confidence interval [CI], 1.07-5.08; p = 0.033), long-term mortality [hazard ratio (HR), 2.11, 95% CI, 1.19-3.74, P = 0.011] and long-term MACE (HR, 1.95, 95% CI, 1.26-3.02, P = 0.003). To further clarify the relationship between the severity of CAD and long-term outcomes, we categorized patients into three groups: zero-vessel disease, single-vessel disease and multi-vessel disease. The long-term mortality (9.7 vs. 14.4 vs. 21.2%, P = 0.045), and long-term MACE (16.8 vs. 22.2 vs. 40.4%, P = 0.001) increased with the number of identified stenosed coronary vessels. Multivariable analysis indicated that, multi-vessel disease was independently associated with long-term mortality (HR, 2.38, 95% CI, 1.16-4.89, P = 0.018) and long-term MACE (HR, 2.79, 95% CI, 1.65-4.73, P = 0.001), compared with zero-vessel disease. Conclusions: CAD was associated with short-term and long-term worse outcomes in patients with acute or subacute TBAD undergoing TEVAR. Furthermore, the severity of CAD was also associated with worse long-term prognosis. Therefore, CAD could be considered as a useful independent predictor for pre-TEVAR risk stratification in patients with TBAD.

[Advances on microbial synthesis of L-proline and trans-4-hydroxy-L-proline].

L-proline (L-Pro) is the only imino acid among the 20 amino acids that constitute biological proteins, and its main hydroxylated product is trans-4-hydroxy-L-proline (T-4-Hyp). Both of them have unique biological activities and play important roles in biomedicine, food and beauty industry. With the in-depth exploration of the functions of L-Pro and T-4-Hyp, the demand for them is gradually increasing. Traditional methods of biological extraction and chemical synthesis are unable to meet the demand of "green, environmental protection and high efficiency". In recent years, synthetic biology has developed rapidly. Through the intensive analysis of the synthetic pathways of L-Pro and T-4-Hyp, microbial cell factories were constructed for large-scale production, which opened a new chapter for the green and efficient production of L-Pro and T-4-Hyp. This paper reviews the application and production methods of L-Pro and T-4-Hyp, the metabolic pathways for microbial synthesis of L-Pro and T-4-Hyp, and the engineering strategies and advances on microbial production of L-Pro and T-4-Hyp, aiming to provide a theoretical basis for the "green bio-manufacturing" of L-Pro and T-4-Hyp and promote their industrial production.

Amide alkaloids characterization and neuroprotective properties of Piper nigrum L.: A comparative study with fruits, pericarp, stalks and leaves.

Piper nigrum L. is commonly used worldwide and its pericarp, stalks, leaves will be major wastes materials. 42 amide alkaloids were identified in black, white pepper and pericarp by UHPLC-LTQ-Orbitrap HRMS method, followed by 40 constituents in stalks and 36 constituents in leaves. 8 amide alkaloids were reported for the first time in P. nigrum. An ultra-high-performance supercritical fluid chromatography (UHPSFC)-MS method was firstly applied to simultaneously determine 9 characteristic constituents (piperine, piperlonguminine, piperanine, pipercallosine, dehydropipernonaline, pipernonatine, retrofractamide B, pellitorine and guineensine). The most abundant compound in each extract was piperine with a concentration from 0.10 to 12.37 mg/g of dry weight. The fruits, pericarp and leaves extracts could improve cell viability in 6-OHDA-induced SK-N-SH and SH-SY5Y cells. The results showed the characteristics of amide alkaloids of different parts of P. nigrum and evaluated their neuroprotective activities.

Phosphorylation of Ago2 is required for its role in DNA double-strand break repair.

Repair of DNA double-strand break (DSB) is critical for the maintenance of genome integrity. A class of DSB-induced small RNAs (diRNAs) has been shown to play an important role in DSB repair. In humans, diRNAs are associated with Ago2 and guide the recruitment of Rad51 to DSB sites to facilitate repair by homologous recombination (HR). Ago2 activity has been reported to be regulated by phosphorylation under normal and hypoxic conditions. However, the role of Ago2 phosphorylation in DNA damage repair is unexplored. Here, we show that S672, S828, T830, and S831 of human Ago2 are phosphorylated in response to ionizing radiation (IR). S672A mutation of Ago2 leads to significant reduction in Rad51 foci formation and HR efficiency. We further show that defective association of Ago2 S672A variant with DSB sites, instead of defects in diRNA and Rad51 binding, may account for decreased Rad51 foci formation and HR efficiency. Our study reveals a novel regulatory mechanism for the function of Ago2 in DNA repair.

Application of ultra-low-dose CT in 3D printing of distal radial fractures.

PURPOSE: To explore the effect of ultra-low-dose computed tomography (CT) on three-dimensional (3D) printing models and the diagnosis of wrist fractures. METHOD: This study enrolled 76 patients with distal radial fractures (DRFs). All patients underwent 320-row detector CT and were divided randomly into two groups. In Group A, 38 patients were scanned with the standard-dose protocol using a tube voltage of 120 kV and current of 100 mA. In Group B, 38 patients were scanned with the ultra-low-dose protocol using a tube voltage of 80 kV and current of 10 mA. For objective image quality assessment, the noise, CT number, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured. Subjectively, two experienced orthopaedic surgeons blinded to the scan parameters evaluated the clarity of the 3D printing model and fracture line using a 3-point scale (the diagnosis was considered acceptable with scores ≥2). The mean radiation dose was calculated. The diagnostic performances for the fractures between the two groups were compared. RESULTS: The effective radiation dose was significantly reduced by 97.1 % in Group B, compared to Group A (0.28 ± 0.05vs. 9.75 ± 2.23 µSv, respectively). Quantitative objective image quality parameters (e.g., CNR, SNR, and CT numbers) were higher in the standard-dose group (p < 0.001). However, there was no difference in subjective scoring of the 3D printing model. Although the fracture line score was higher in Group A (2.92±0.27 vs. 2.16 ± 0.37; p < 0.001), the diagnostic performance of the two groups was consistent (all scores ≥2). There were no statistically significant differences in the sensitivity, specificity or accuracy between standard-dose group and ultra-low-dose group. CONCLUSIONS: The ultra-low-dose protocol effectively reduced the radiation dose by 97.1 %, while maintaining the image quality for diagnosis of DRFs. Therefore, this protocol can meet the needs of 3D printing models for preoperative assessments.

Learning from SARS: Return and volatility connectedness in COVID-19.

Using a sample of the G20 countries, we examine the impact of COVID-19 on stock return and volatility connectedness, and whether the connectedness measures behave differently for countries with SARS 2003 experience. We find that both stock return and volatility connectedness increase across the phases of the COVID-19 pandemic which is more pronounced as the severity of the pandemic builds up. However, the degree of connectedness is significantly lower in countries with SARS 2003 death experience. Our results are robust to different measures of COVID-19 severity and controlling for a number of cross-country differences in economic development.