Endoplasmic Reticulum-Targeting AIE Photosensitizers to Boost Immunogenic Cell Death for Immunotherapy of Bladder Carcinoma.

Bladder cancer is characterized by high rates of recurrence and multifocality. Immunogenic cell death (ICD) of cancer cells has emerged as a promising strategy to improve the immunogenicity of tumor cells for enhanced cancer immunotherapy. Although photosensitizer-based photodynamic therapy (PDT) has been validated as capable of inducing ICD in cancer cells, the photosensitizers with a sufficient ICD induction ability are still rare, and there have been few reports on the development of advanced photosensitizers to strongly evoke the ICD of bladder cancer cells for eliciting potent antitumor immune responses and eradicating bladder carcinoma in situ. In this work, we have synthesized a new kind of endoplasmic reticulum (ER)-targeting aggregation-induced emission (AIE) photosensitizer (named DPASCP-Tos), which could effectively anchor to the cellular ER and trigger focused reactive oxygen species (ROS) production within the ER, thereby boosting ICD in bladder cancer cells. Furthermore, we have demonstrated that bladder cancer cells killed by ER-targeted PDT could serve as a therapeutic cancer vaccine to elicit a strong antitumor immunity. Prophylactic vaccination of the bladder cancer cells killed by DPASCP-Tos under light irradiation promoted the maturation of dendritic cells (DCs) and the expansion of tumor antigen-specific CD8+ T cells in vivo and protected mice from subsequent in situ bladder tumor rechallenge and extended animal survival. In summary, the ER-targeted AIEgens developed here significantly amplified the ICD of bladder cells through focused ROS-based ER oxidative stress and transformed bladder cancer cells into the therapeutic vaccine to enhance immunogenicity against orthotopic bladder cancer, providing valuable insights for bladder carcinoma treatment.

Enhancing NIR-II Imaging and Photothermal Therapy for Improved Oral Cancer Theranostics by Combining TICT and Aggregation-Induced Emission.

In the treatment process of cancers like oral cancer, it is necessary to employ extensive surgical resection to achieve cancer eradication. However, this often results in damage to crucial functions such as chewing and speaking, leading to a poorer prognosis and a reduced quality of life. To address this issue, a multifunctional theranostic agent named MBPN-T-BTD has been developed by precisely modulating the excitation state energy distribution in the radiative/nonradiative decay pathways using the characteristics of twisted intramolecular charge transfer and aggregation-induced emission. This agent outperforms clinically utilized indocyanine green (ICG) in various aspects, including the second near-infrared window (NIR-II, 1000-1700 nm) fluorescence (FL) and photothermal conversion efficiency (PCE). Its nanoparticle form (BTB NPs) can be effectively used for high-contrast delineation of lymph node mapping and tongue and floor of mouth cancers using NIR-II FL, enabling surgeons to achieve more precise and thorough tumor clearance. For tumors located in close proximity to vital organs such as the tongue, the exceptional PCE (71.96%) of BTB NPs allows for targeted photothermal ablation with minimal damage to peripheral healthy tissues. This contribution provides a safer and more effective paradigm for minimally invasive or noninvasive treatment of oral cancer, ensuring the preservation of normal organ functions and showing potential for improving the overall prognosis and quality of life for cancer patients.

Radiomics and Ki-67 index predict survival in clear cell renal cell carcinoma.

OBJECTIVE: To develop and validate predictive models based on Ki-67 index, radiomics, and Ki-67 index combined with radiomics for survival analysis of patients with clear cell renal cell carcinoma. METHODS: This study enrolled 148 patients who were pathologically diagnosed as ccRCC between March 2010 and December 2018 at our institute. All tissue sections were collected and immunohistochemical staining was performed to calculate Ki-67 index. All patients were randomly divided into the training and validation sets in a 7:3 ratio. Regions of interests (ROIs) were segmented manually. Radiomics features were selected from ROIs in unenhanced, corticomedullary, and nephrographic phases. Multivariate Cox models based on the Ki-67 index and radiomics and univariate Cox models based on the Ki-67 index or radiomics alone were built; the predictive power was evaluated by the concordance (C)-index, integrated area under the curve, and integrated Brier Score. RESULTS: Five features were selected to establish the prediction models of radiomics and combined model. The C-indexes of Ki-67 index model, radiomics model, and combined model were 0.741, 0.718, and 0.782 for disease-free survival (DFS); 0.941, 0.866, and 0.963 for overall survival, respectively. The predictive power of combined model was the best in both training and validation sets. CONCLUSION: The survival prediction performance of combined model was better than Ki-67 model or radiomics model. The combined model is a promising tool for predicting the prognosis of patients with ccRCC in the future. ADVANCES IN KNOWLEDGE: Both Ki-67 and radiomics have showed giant potential in prognosis prediction. There are few studies to investigate the predictive ability of Ki-67 combined with radiomics. This study intended to build a combined model and provide a reliable prognosis for ccRCC in clinical practice.

Nomogram Based on Preoperative Absolute Lymphocyte Count to Predict Local Recurrence in Patients with Non-Small Cell Lung Cancer After Microwave Ablation.

Purpose: This study aims to investigate the prognostic value of preoperative absolute lymphocyte count (preALC) for non-small cell lung cancer (NSCLC) after microwave ablation (MWA) and build a combined nomograph with clinical features to predict the local recurrence. Patients and Methods: A total of 118 NSCLC patients who underwent microwave ablation were enrolled in this study. The median local recurrence-free survival (LRFS) was 35.5 months. Independent prognostic factors obtained by multivariate analysis were included in the prediction model. The prognostic value of the model was assessed by the area under the time-dependent receiver operating characteristic curve (T-AUC). Results: Histological subtype and preALC were independent risk factors for local relapse-free survival. According to the time-dependent receiver operating characteristic curve (T-ROC), the optimal cut-off value of preALC was 1.965×109/L, the sensitivity was 0.837, and the specificity was 0.594. The area under the T-ROC curve (AUC) of preALC was 0.703. To establish a nomogram to predict the local recurrence rate of NSCLC after MWA based on the prognostic factors revealed by Cox regression. Conclusion: Preoperative lymphocyte count reduction is associated with poor prognosis of NSCLC. The nomogram model combined with preALC can provide a good individualized prediction of local recurrence after microwave ablation.

A Fluorinated Supramolecular Self-Assembled Peptide as Nanovaccine Adjuvant for Enhanced Cancer Vaccine Therapy.

Adjuvants play an important role in enhancing vaccine-induced immune protection. Adequate cellular uptake, robust lysosomal escape, and subsequent antigen cross-presentation are critical steps for vaccine adjuvants to effectively elicit cellular immunity. Here, a fluorinated supramolecular strategy to generate a series of peptide adjuvants by using arginine (R) and fluorinated diphenylalanine peptide (DP) is adopted. It is found that the self-assembly ability and antigen-binding affinity of these adjuvants increase with the number of fluorine (F) and can be regulated by R. By comparison, 4RDP(F5) shows the strongest binding affinity with model antigen ovalbumin (OVA) and the best performance in dendritic cells maturation and antigen's lysosomal escape, which contributes to the subsequent antigen cross-presentation. As a consequence, 4RDP(F5)-OVA nanovaccine generates a strong cellular immunity in a prophylactic OVA-expressing EG7-OVA lymphoma model, leading to long-term immune memory for resisting tumor challenge. What's more, 4RDP(F5)-OVA nanovaccine in combination with anti-programmed cell death ligand-1 (anti-PD-L1) checkpoint blockade could effectively elicit anti-tumor immune responses and inhibit tumor growth in a therapeutic EG7-OVA lymphoma model. Overall, this study demonstrates the simplicity and effectiveness of fluorinated supramolecular strategies for constructing adjuvants and might provide an attractive vaccine adjuvant candidate for cancer immunotherapy.

Reconfigurable Peptide Analogs of Apolipoprotein A-I Reveal Tunable Features of Nanodisc Assembly.

Nanodisc (ND)-forming membrane scaffold proteins or peptides developed from apolipoprotein A-I (apoA-I) have led to considerable promise in structural biology and therapeutic applications. However, the rationale and regularity characteristics in peptide sequence design remain inconclusive. Here, we proposed a consensus-based normalization approach through the reversed engineering of apoA-IΔ1-45 to design reconfigurable apoA-I peptide analogs (APAs) for tunable ND assembly. We present extensive morphological validations and computational simulation analyses on divergent APA-NDs that are generated by our method. Fifteen divergent APAs were generated accordingly to study the assembly machinery of NDs. We show that APA designs exhibit multifactorial influence in terms of varying APA tandem repeats, sequence composition, and lipid-to-APA ratio to form tunable diameters of NDs. There is a strong positive correlation between DMPC-to-APA ratios and ND diameters. Longer APA with more tandem repeats tends to yield higher particle size homogeneity. Our results also suggest proline is a dispensable residue for the APA-ND formation. Interestingly, proline-rich substitution not only provides an inward-bending effect in forming smaller NDs but also induces the cumulative chain flexibility that enables larger ND formation at higher lipid ratios. Additionally, proline-tryptophan residues in APAs play a dominant role in forming larger NDs. Molecular simulation shows that enriched basic and acidic residues in APAs evoke abundant hydrogen-bond and salt bridge networks to reinforce the structural stability of APA-NDs. Together, our findings provide a rational basis for understanding APA design. The proposed model could be extended to other apolipoproteins for desired ND engineering.

Ferroptosis: From regulation of lipid peroxidation to the treatment of diseases.

Ferroptosis is a regulated cell death mainly manifested by iron-dependent lipid peroxide accumulation. The leading cause of ferroptosis is the imbalance of intracellular oxidative systems (e.g., LOXs, POR, ROS) and antioxidant systems (e.g., GSH/GPx4, CoQ10/FSP1, BH4/GCH1), which is regulated by a complex network. In the past decade, this metabolic network has been continuously refined, and the links with various pathophysiological processes have been gradually established. Apoptosis has been regarded as the only form of regulated cell death for a long time, and the application of chemotherapeutic drugs to induce apoptosis of cancer cells is the mainstream method. However, studies have reported that cancer cells' key features are resistance to apoptosis and chemotherapeutics. For high proliferation, cancer cells often have very active lipid metabolism and iron metabolism, which pave the way for ferroptosis. Interestingly, researchers found that drug-resistant or highly aggressive cancer cells are more prone to ferroptosis. Therefore, ferroptosis may be a potential strategy to eliminate cancer cells. In addition, links between ferroptosis and other diseases, such as neurological disorders and ischemia-reperfusion injury, have also been found. Understanding these diseases from the perspective of ferroptosis may provide new insights into clinical treatment. Herein, the metabolic processes in ferroptosis are reviewed, and the potential mechanisms and targets of ferroptosis in different diseases are summarized.

Melittin Tryptophan Substitution with a Fluorescent Amino Acid Reveals the Structural Basis of Selective Antitumor Effect and Subcellular Localization in Tumor Cells.

Melittin is a membrane-active peptide with strong anticancer activity against various cancers. Despite decades of research, the role of the singular Trp in the anticancer activity and selectivity of melittin remains poorly understood. Here, we propose a theranostic solution based on the substitution of Trp19 with a noncanonical fluorescent amino acid (DapAMCA). The introduction of DapAMCA residue in melittin stabilized the helical structure of the peptide, as evaluated by circular dichroism spectra and molecular dynamics simulations. In vitro hemolytic and anticancer activity assays revealed that introducing DapAMCA residue in melittin changed its mode of action with the cell membrane, resulting in reduced hemolytic toxicity and an improved the selectivity index (SI), with up to a five-fold increase compared to melittin. In vitro fluorescence imaging of DapAMCA-labeled melittin (MELFL) in cancer cells demonstrated high membrane-penetrating activity, with strong nuclear and nucleolar localization ability. These findings provide implications for novel anticancer therapies based on Trp-substituted designs and nuclear/nucleolar targeted therapy.

An in Silico Approach to Reveal the Nanodisc Formulation of Doxorubicin.

Molecular dynamic behaviors of nanodisc (ND) formulations of free doxorubicin (DOX) and DOX conjugated lipid prodrug molecules were investigated by molecular dynamics (MD) simulations. We have unveiled how formulation design affects the drug release profile and conformational stability of ND assemblies. Our simulation results indicate that free DOX molecules loaded in the ND system experienced rapid dissociation due to the unfavorable orientation of DOX attached to the lipid surface. It is found that DOX tends to form aggregates with higher drug quantities. In contrast, lipidated DOX-prodrugs incorporated in ND formulations exhibited sufficient ND conformational stability. The drug loading capacity is dependent on the type of lipid molecules grafted on the DOX-prodrug, and the drug loading quantities in a fixed area of NDs follow the order: DOX-BMPH-MP > DOX-BMPH-TC > DOX-BMPH-PTE. To gain further insight into the dynamic characteristics of ND formulations governed by different kinds of lipidation, we investigated the conformational variation of ND components, intermolecular interactions, the solvent accessible surface area, and individual MSP1 residue flexibility. We found that the global conformational stability of DOX-prodrug-loaded ND assemblies is influenced by the molecular flexibility and lipidated forms of DOX-prodrug. We also found that the spontaneous self-aggregation of DOX-prodrugs with increasing quantities on ND could reduce the membrane fluidity and enhance the conformational stability of ND formulations.

Intravascular ultrasound-guided percutaneous coronary intervention for patients with coronary bifurcation lesions: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Intravascular ultrasound (IVUS) could take on a vital position when angiographic images are not clear enough to be precisely visualized or measured by computer-aided technology. This meta-analysis was designed to compare the benefits of IVUS-guided and angiography-guided percutaneous coronary intervention(PCI) strategies for improving clinical outcomes. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for articles published from inception to 13th October, 2019. A comparative study of IVUS-guided and angiography-guided PCI strategies for patients with coronary bifurcation lesions was retrieved. The early endpoint events (≤1 year) and the late endpoint events (>1 years) were determined according to the follow-up time. The former included cardiac death, target lesion or vessel revascularization, stent thrombus, and major adverse cardiac events, while the latter included cardiac death. Statistical software Review Manager Version 5.3 was performed for meta-analysis. RESULTS: Five studies involving7,830 patients with coronary bifurcation lesions were included in this meta-analysis, the incidence of major adverse cardiac events for IVUS-guided strategy in patients with coronary bifurcation lesions were lower than those of patients with angiography-guided strategy at the early follow-up(OR = 0.55, 95% CI 0.42 - 0.70, P < .0001).Meanwhile, cardiac death, target vessel or target lesion revascularization, stent thrombosis were not statistically significant(OR = 0.68, 95% CI 0.34 - 1.35, P = .27; OR = 0.78, 95% CI 0.59 - 1.05, P = .10; OR = 0.36, 95% CI 0.12-1.04, P = .06).However, significant differences in cardiac death between IVUS-guided and angiographic-guided strategies were observed in the late follow - up (OR = 0.36, 95% CI 0.23 - 0.57, P < .00001). CONCLUSION: The IVUS-guided PCI strategy was associated with more clinical benefits compared with angiography-guided PCI strategy in patients with coronary bifurcation lesions. These findings suggest that the IVUS-guided PCI strategy can be recommended as an optimization in this kind of patients.

Reveal the interaction mechanism of five old drugs targeting VEGFR2 through computational simulations.

VEGFR2, vascular endothelial growth factor receptor 2, plays an important role in anti-angiogenesis and is an effective target for inhibiting tumor cell proliferation and metastasis. Many small molecule inhibitors have so far exhibited fine therapeutic effects but do not rule out some adverse reactions. From the perspective of the new use of old drugs, we use a combination of two different docking methods, molecular dynamics simulations and quantum-chemical calculations to acquire potential anti-angiogenesis inhibitors from the library of FDA-approved drugs. We attain five FDA-approved old drugs from Drugbank as potential inhibitors against VEGFR2. Therein, the anti-tumor effects of three compounds, including vilazodone (psychiatric drug), pranlukast and zafirlukast (asthma drugs), have been reported by previous experiments but no anti-tumor data is available for the other two compounds, including antrafenine (analgesic and anti-inflammatory drug) and iloperidone (psychiatric drug). These five compounds exhibit more stable interaction than sorafenib as a market-oriented drug targeting VEGFR2. In parallel, there is a most stable interaction for zafirlukast while a weakest interaction for iloperidone with VEGFR2. We show that these five compounds bind with the hydrophobic cavity of VEGFR2, then forming hydrogen bond interactions with three key residues, Glu-885, Cys-919 and Asp-1046. Lys-868 and Phe-1047 play an important role in stabilizing the interaction conformation. The binding poses of pranlukast and vilazodone are similar to that of sorafenib, whereas antrafenine and zafirlukast act differently from sorafenib, focusing on the direction difference of the respective ring structure. This work may help to develop new and effective anti-angiogenic inhibitors.

Revealing the Mechanism of EGCG, Genistein, Rutin, Quercetin, and Silibinin Against hIAPP Aggregation via Computational Simulations.

To inhibit hIAPP aggregation and reduce toxicity of its oligomers are one of the potential strategies for the treatment of Type 2 diabetes (T2D). It has been reported that there is an effective inhibitory effect on hIAPP aggregation by five natural flavonoids, including Genistein, Rutin, Quercetin, Epigallocatechin gallate (EGCG), and Silibinin, which are widely found in our daily food. However, the detailed mechanisms to inhibit hIAPP aggregation remain unclear. Here, we explore the mechanisms of the five flavonoids against hIAPP aggregation by molecular docking and molecular dynamics simulations. We show that these flavonoids can disaggregate Chain A and Chain B of hIAPP to reduce the extended conformation by binding with two regions of hIAPP, Leu12-Ala13-Asn14 and Asn31-Val32-Gly33-Ser34-Asn35, with the inhibitory ability of Genistein > Rutin > Quercetin > EGCG > Silibinin. These five compounds exhibit a common mechanism for disaggregation of the hIAPP pentamer; that is, they loosen the two nearest peptide chains to potentially destroy the hIAPP oligomer. Mutations of eight key residues remarkably affected by the flavonoids indicate that the secondary structures of the hIAPP pentamer change from ß-sheet to be random coil, thereby to destroy its structural stability; moreover, the 28th (Ser), 12th (Leu) and 32nd (Val) amino acids exhibit significant effects on structural stability of the hIAPP pentamer, providing an important hint that these amino acids can be considered as potential targets for design of new candidate inhibitors against hIAPP oligomers. This work is beneficial to understanding of mechanism of these inhibits against hIAPP aggregation and will facilitate screening, modification, and design of new inhibitors.

De-escalation versus standard dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

Switching from a potent P2Y12 blocker to clopidogrel is not uncommon for antiplatelet therapy in patients undergoing percutaneous coronary intervention. This meta-analysis aimed to investigate the efficacy and safety of this de-escalation strategy. Medical literature databases were searched for analysis comparing continued potent antiplatelet therapy and switching to clopidogrel with no language restrictions from inception to 07/May/2018. The primary endpoints of major adverse cardiovascular events (MACE) and major bleeding together with additional efficacy outcomes were assessed by random-effects and fixed-effects meta-analysis. A total of 17 896 patients in 13 studies were eligible for analysis, while 17 579 (98.2%) patients presented as acute coronary syndrome and 4105 (23%) patients received the de-escalation therapy. Incidence of MACE was virtually identical in both de-escalation and standard potent antiplatelet therapy groups (odds ratio 0.91, 95% CI 0.73-1.14; P = 0.43). Insignificant difference was also observed in major bleeding (0.99, 0.62-1.60; P = 0.97), all-cause death (0.95, 0.61-1.46; P = 0.81), cardiovascular death (0.66, 0.31-1.42; P = 0.29), myocardial infarction (1.12, 0.80-1.58; P = 0.51), stent thrombosis (1.09, 0.50-2.36; P = 0.83), unplanned revascularization (1.09, 0.83-1.41; P = 0.54), and stroke (1.16, 0.62-2.19; P = 0.64). In conclusion, de-escalation of antiplatelet therapy is associated with nonsignificant differences in both ischemic events and major bleeding compared with standard potent antiplatelet therapy in patients undergoing percutaneous coronary intervention. The feasibility and even superiority of this strategy need to be elucidated by further randomized trials.

Design, synthesis and evaluation of a novel fluorescent probe to accurately detect H2S in hepatocytes and natural waters.

Design and synthesis of fluorescent probe with fast response, excellent water solubility and good hepatocyte-targeting capacity to detect hydrogen sulfide (H2S) in hepatocytes and water samples is of great significance. Here, a novel fluorescent probe QL-Gal-N3 for detection of H2S was designed and synthesized based on H2S-mediated azide reduction strategy. This sensor demonstrated low toxicity, fast response (within 1 min), high selectivity and low detection limit (as low as 126 nM in water) for the detection of H2S. HeLa, A549 and HepG-2 cells were chosen to investigate the hepatocyte-targeting ability of QL-Gal-N3 respectively. The results indicated that the specific recognition of ASGPR over-expressed in hepatocytes by galactose group was an important reason for the good targeting ability of probe QL-Gal-N3. Furthermore, due to the introduction of glycosyl moiety, the water solubility of fluorescent probe was enhanced obviously. It was successfully applied for the detection of H2S in environmental water samples including river water, tap water, lake water and waste water.

Comparison of early and delayed invasive strategies in short-medium term among patients with non-ST segment elevation acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: An invasive approach is recommended as the treatment of patients with non-ST elevated acute coronary syndromes (NSTE-ACS). However, it remains unclear that the optimal time of angiography and intervention for patients with NSTE-ACS at present. This study was designed to compare the effect of early and delayed invasive strategies on short-medium term prognosis in patients with those. METHODS: Pubmed, Cochrane Library and Embase were searched up to Dec-30-2018. Randomized clinical trials comparing an early versus a delayed invasive strategy in patients with NSTE-ACS were included. The primary endpoint (all-cause death and recurrent myocardial infarction) and secondary endpoint (major bleeding and recurrent revascularization), as well as composite endpoint were assessed by random or fixed effected meta-analysis with software RevMan 5.3 version after short-medium term follow up. RESULT: A total of six randomized clinical trials involving 4,277 early or delayed invasive strategies patients with NSTE-ACS were included in the meta-analysis. Time to coronary angiography varied from 0.5 to 24 h in the early invasive strategy and from 18.6 to 72 h in the delayed invasive strategy. There was a statistical difference in the primary endpoint of all-cause death among patients with NSTE-ACS between early and delayed invasive strategies (4.6% vs 6%; OR:0.76; 95% CI:0.58 to 1.00; P = 0.05; I2 = 0%), but not for recurrent myocardial infarction (6.0% vs 6.3%; OR: 0.94; 95% CI: 0.55 to 1.61; P = 0.82; I2 = 60%). The major bleeding in patients with NSTE-ACS was similar between both invasive strategies (2.7% vs 3.1%; OR:0.88; 95% CI:0.59 to 1.31; P = 0.54; I2 = 0%). However, the composite endpoint in the early invasive strategy patients with NSTE-ACS was significantly lower than that of the delayed invasive strategy (10.9% vs 13.9%; OR:0.76; 95% CI:0.63 to 0.92; P = 0.006; I2 = 0%), and the recurrent revascularization between both strategies was just the opposite (8.7% vs 5.9%; OR:1.5; 95%CI:1.15 to 1.97; P = 0.003; I2 = 0%). CONCLUSION: The systematic review and meta-analysis demonstrated that the early invasive strategy had a beneficial trend on all-cause death and significantly reduced the composite endpoint in patients with NSTE-ACS, but increased the rate of revascularization. These data could provide a solution for patients with those.

Drug-coated balloon versus drug-eluting stent in de novo small coronary vessel disease: A systematic review and meta-analysis.

BACKGROUND: Drug-coated balloon as a novel therapeutic strategy has been used to treat restenosis in cases of bare metal and drug-eluting stents. However, evidence of its safety and efficacy is scarce in de novo small coronary artery vessel disease. This meta-analysis aimed to compare the safety and efficacy of the drug-coated balloon and the drug-eluting stent. METHODS: The PubMed, EMBASE, Web of Science, and Cochrane library databases were searched for studies published up to October 17, 2018. Studies comparing the drug-coated balloon with the drug-eluting stent strategy in patients with de novo small coronary artery vessel disease (reference diameter, <3 mm) were identified. The clinical outcomes were nonfatal myocardial infarction, cardiac death, all-cause death, target lesion revascularization, and target-vessel revascularization. Data were analyzed using the statistical software RevMan (version 5.3). Fixed effects models were performed to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Sensitivity analyses were used to detect potential sources of heterogeneity, while subgroup analyses were implemented to assess the differential effects. RESULTS: Three randomized controlled trials and 3 nonrandomized controlled studies were identified. Six studies including a total of 1800 patients compared the differences between the drug-coated balloon and the drug-eluting stent strategies in patients with de novo small coronary artery vessel disease. The results indicated that the drug-coated balloon strategy was associated with a significant reduction in nonfatal myocardial infarction (OR 0.53, 95% CI 0.31-0.90, P = .02) compared with the drug-eluting stent strategy, while insignificant inter-strategy differences were observed in cardiac death (OR 1.56, 95% CI 0.73-3.33, P = .25), all-cause death (OR 0.56, 95% CI 0.25-1.23, P = .15), target lesion revascularization (OR 1.24, 95% CI 0.73-2.1, P = .43), and target-vessel revascularization (OR 0.95, 95% CI 0.59-1.52, P = .84). CONCLUSIONS: This meta-analysis suggests that the drug-coated balloon strategy is noninferior to the drug-eluting stent strategy, delivering a good outcome in nonfatal myocardial infarction, and can be recommended as an optimal treatment strategy in patients with de novo small coronary artery vessel disease. Larger randomized controlled studies with longer follow-up periods are needed to further confirm the benefits of the drug-coated balloon strategy.

The interaction mechanism of oligopeptides containing aromatic rings with ß-cyclodextrin and its derivatives.

We investigate the formation mechanism of supramolecular complexes of four antioxidant oligopeptides (YW, WY, WYS, and WYSL) with ß-cyclodextrin (ß-CD), hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and 6-O-α-maltosyl-ß-cyclodextrin (M-ß-CD) by combined computational and experimental methods. The formation of complexes is determined by UV, IR and DSC, and the rank-ordered acquired stability of the complexes is as follows: WYSL/HP-ß-CD > WYS/HP-ß-CD > WY/HP-ß-CD > YW/M-ß-CD > YW/HP-ß-CD > YW/ß-CD. The 1H NMR analysis and molecular docking results reveal that the aromatic rings of these oligopeptides are embedded into the cavities of the studied ß-CD and its derivatives, indicating that hydrophobic interaction is a major driving force for the formation of the complexes. We also demonstrate that H-bonds play a key role in maintaining the supramolecular complexes. In addition, the results of the antioxidant assay indicate that the radical scavenging capacity of the oligopeptides is enhanced by the CD-based inclusion.

Modified double-stent strategy may be an optimal choice for coronary bifurcation lesions: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The modified double-stent and provisional stenting strategies have been widely used in patients with coronary bifurcation lesions, but what is the optimization has not been clearly defined. This meta-analysis is to elucidate the benefits from modified double-stent and provisional stenting strategies in patients with coronary bifurcation lesions. METHODS: Electronic databases were searched to identify studies comparing the modified double-stent and provisional stenting strategies in patients with coronary bifurcation lesions. The clinical outcomes were divided into early (≤6 months) and late (>6 months) events according to the follow-up duration. The early endpoints included cardiac death, myocardial infarction, target lesion revascularization or target vessel revascularization, and major adverse cardiac events (MACE), and the late endpoints also include stent thrombosis in addition to the early endpoints index. The angiographic endpoint was in-stent restenosis. Data were analyzed by the statistical software RevMan (version 5.3). RESULTS: A total of 6 studies involving 1683 patients with coronary bifurcation lesions were included in this meta-analysis, which found that the modified double-stent strategy was associated with a lower risk of cardiac death (odds ratio [OR] = 0.29, 95% confidence intervals [CI] 0.11-0.78, P = .01), myocardial infarction (OR = 0.41, 95% CI 0.21-0.82, P = .01), target lesion revascularization or target vessel revascularization (OR = 0.31, 95% CI 0.15-0.63, P = .001), and MACE (OR = 0.41, 95% CI 0.22-0.74, P = .003) compared with provisional stenting in the early follow-up endpoint events, while the risk of cardiac death and stent thrombosis were similar between both strategies (OR = 0.59, 95% CI 0.31-1.10, P = .09; and OR = 0.62, 95% CI 0.34-1.15, P = .13; respectively) in the late follow-up endpoint events. There were significant differences between both strategies in myocardial infarction (OR = 0.42, 95% CI 0.24-0.75, P = .003), MACE (OR = 0.44, 95% CI 0.31-0.62, P < .00001), and target lesion revascularization or target vessel revascularization (OR 0.35, 95% CI 0.25-0.49, P < .00001) between both strategies in the late follow-up endpoint events. The risk of in-stent restenosis favored the modified double-stent strategy (OR 0.29, 95% CI 0.20-0.43, P < .00001). CONCLUSION: The modified double-stent strategy is associated with excellent clinical and angiographic outcomes except for the occurrence of cardiac death and stent thrombosis late-term outcome compared with provisional stenting strategy in patients with coronary bifurcation lesions. These findings suggest that the modified double-stent strategy can be recommended as an optimization in patients with coronary bifurcation lesions.

Genetic diversity of internalin genes in the ascB-dapE locus among Listeria monocytogenes lineages III and IV strains.

Listeria monocytogenes is an important foodborne pathogen encompassing four phylogenetic lineages. Lineages III and IV are rare, but have been reported to show considerable biodiversity, providing important clues for the evolutionary history in Listeria. In this study, analysis of the ascB-dapE locus reveals genetic diversity in lineages III and IV, and is consistent with the classification of sublineages. Four of the six genetic patterns (two of sublineage IIIC and two of lineage IV) are specific to these two lineages. The ascB-dapE locus suggests a hot spot for genome diversification, and serves as an attractive molecular marker for better understanding of the biodiversity and population structure of lineages III and IV strains.

Genetic organization of ascB-dapE internalin cluster serves as a potential marker for Listeria monocytogenes sublineages IIA, IIB, and IIC.

Listeria monocytogenes is an important foodborne pathogen that comprises four genetic lineages: I, II, III, and IV. Of these, lineage II is frequently recovered from foods and environments and responsible for the increasing incidence of human listeriosis. In this study, the phylogenetic structure of lineage II was determined through sequencing analysis of the ascB-dapE internalin cluster. Fifteen sequence types proposed by multilocus sequence typing based on nine housekeeping genes were grouped into three distinct sublineages, IIA, IIB, and IIC. Organization of the ascBdapE internalin cluster could serve as a molecular marker for these sublineages, with inlGHE, inlGC2DE, and inlC2DE for IIA, IIB, and IIC, respectively. These sublineages displayed specific genetic and phenotypic characteristics. IIA and IIC showed a higher frequency of recombination (rho/theta). However, recombination events had greater effect (r/m) on IIB, leading to its high nucleotide diversity. Moreover, IIA and IIB harbored a wider range of internalin and stress-response genes, and possessed higher nisin tolerance, whereas IIC contained the largest portion of low-virulent strains owing to premature stop codons in inlA. The results of this study indicate that IIA, IIB, and IIC might occupy different ecological niches, and IIB might have a better adaptation to a broad range of environmental niches.