The role of cardiac resident macrophage in cardiac aging.

Advancements in longevity research have provided insights into the impact of cardiac aging on the structural and functional aspects of the heart. Notable changes include the gradual remodeling of the myocardium, the occurrence of left ventricular hypertrophy, and the decline in both systolic and diastolic functions. Macrophages, a type of immune cell, play a pivotal role in innate immunity by serving as vigilant agents against pathogens, facilitating wound healing, and orchestrating the development of targeted acquired immune responses. Distinct subsets of macrophages are present within the cardiac tissue and demonstrate varied functions in response to myocardial injury. The differentiation of cardiac macrophages according to their developmental origin has proven to be a valuable strategy in identifying reparative macrophage populations, which originate from embryonic cells and reside within the tissue, as well as inflammatory macrophages, which are derived from monocytes and recruited to the heart. These subsets of macrophages possess unique characteristics and perform distinct functions. This review aims to summarize the current understanding of the roles and phenotypes of cardiac macrophages in various conditions, including the steady state, aging, and other pathological conditions. Additionally, it will highlight areas that require further investigation to expand our knowledge in this field.

COVID-19 and Acute Cardiac Injury: Clinical Manifestations, Biomarkers, Mechanisms, Diagnosis, and Treatment.

PURPOSE OF REVIEW: This review aims to comprehensively explore the clinical characteristics of COVID-19-related cardiac injury and examine the potential mechanisms underlying cardiac injury in patients affected by COVID-19. RECENT FINDINGS: The COVID-19 pandemic has primarily been associated with severe respiratory symptoms. However, emerging evidence has indicated that a significant number of COVID-19 patients also experience myocardial injury, leading to conditions such as acute myocarditis, heart failure, acute coronary syndrome, and arrhythmias. The incidence of myocardial injury is notably higher in patients with preexisting cardiovascular diseases. Myocardial injury often manifests with elevated levels of inflammation biomarkers, as well as abnormalities observed on electrocardiograms and echocardiograms. COVID-19 infection has been found to be associated with myocardial injury, which can be attributed to several pathophysiological mechanisms. These mechanisms include injury caused by hypoxia, resulting from respiratory compromise, a systemic inflammatory response triggered by the infection, and direct attack on the myocardium by the virus itself. Furthermore, the angiotensin-converting enzyme 2 (ACE2) receptor plays a crucial role in this process. Early recognition, prompt diagnosis, and a comprehensive understanding of the underlying mechanisms are essential for effectively managing and reducing the mortality associated with myocardial injury in COVID-19 patients.

Phosphatidylethanolamine N-methyltransferase: from Functions to Diseases.

Locating on endoplasmic reticulum and mitochondria associated membrane, Phosphatidylethanolamine N-methyltransferase (PEMT), catalyzes phosphatidylethanolamine methylation to phosphatidylcholine. As the only endogenous pathway for choline biosynthesis in mammals, the dysregulation of PEMT can lead to imbalance of phospholipid metabolism. Dysregulation of phospholipid metabolism in the liver or heart can lead to deposition of toxic lipid species that adversely result in dysfunction of hepatocyte/cardiomyocyte. Studies have shown that PEMT-/- mice increased susceptibility of diet-induced fatty liver and steatohepatitis. However, knockout of PEMT protects against diet-induced atherosclerosis, diet-induced obesity, and insulin resistance. Thus, novel insights to the function of PEMT in various organs should be summarized. Here, we reviewed the structural and functional properties of PEMT, highlighting its role in the pathogenesis of obesity, liver diseases, cardiovascular diseases, and other conditions.

Urban growth boundaries optimization under low-carbon development: Combining multi-objective programming and patch cellular automata models.

Urban Growth Boundaries (UGBs) are a tool to control urban sprawl. However, the way to optimize future urban land uses and fix their boundaries is not clear. This paper presents a new framework to delimit UGBs while accounting for ecological, economic, and carbon storage benefits. Aggregate land-use constraints are included in a multi-objective optimization algorithm to capture non-inferior solutions on the Pareto Surface (PS) under different objective scenarios. A patch-level cellular automata simulation model is then used to spatially allocate these land uses, followed by a new two-step adjustment method to delineate the UGBs. This modeling is applied to Wuhan, China. The results show that: (1) One district (Caidian) will have a strong economic growth under low-carbon development. (2) The maximization of carbon storage reduces losses in ecological benefits, suggesting that carbon storage be considered in urban growth planning. (3) The combined model framework and two-step boundary adjustment method can help urban planners define different UGB scenarios and make science-based policy decisions.

Association between PM2.5-bound metals and pediatric respiratory health in Guangzhou: An ecological study investigating source, health risk, and effect.

Background: The adverse effects of 2.5-µm particulate matter (PM2.5) exposure on public health have become an increasing concern worldwide. However, epidemiological findings on the effects of PM2.5-bound metals on children's respiratory health are limited and inconsistent because PM2.5 is a complicated mixture. Objectives: Given the vulnerability of children's respiratory system, aim to pediatric respiratory health, this study evaluated the potential sources, health risks, and acute health effects of ambient PM2.5-bound metals among children in Guangzhou, China from January 2017 to December 2019. Methods: Potential sources of PM2.5-bound metals were detected using positive matrix factorization (PMF). A health risk assessment was conducted to investigate the inhalation risk of PM2.5-bound metals in children. The associations between PM2.5-bound metals and pediatric respiratory outpatient visits were examined with a quasi-Poisson generalized additive model (GAM). Results: During 2017-2019, the daily mean concentrations of PM2.5 was 53.39 µg/m3, and the daily mean concentrations of PM2.5-bound metals range 0.03 ng/m3 [thorium (Th) and beryllium (Be)] from to 396.40 ng/m3 [iron (Fe)]. PM2.5-bound metals were mainly contributed by motor vehicles and street dust. PM2.5-bound arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr)(VI), nickel (Ni), and lead (Pb) were found to pose a carcinogenic risk (CR). A quasi-Poisson GAM was constructed that showed there were significant associations between PM2.5 concentrations and pediatric outpatient visits for respiratory diseases. PM2.5 was significantly associated with pediatric outpatient visits for respiratory diseases. Moreover, with a 10 µg/m3 increase in Ni, Cr(VI), Ni, and As concentrations, the corresponding pediatric outpatient visits for respiratory diseases increased by 2.89% (95% CI: 2.28-3.50%), acute upper respiratory infections (AURIs) increased by 2.74% (2.13-3.35%), influenza and pneumonia (FLU&PN) increased by 23.36% (20.09-26.72%), and acute lower respiratory infections (ALRIs) increased by 16.86% (15.16-18.60%), respectively. Conclusions: Our findings showed that PM2.5 and PM2.5-bound As, Cd, Co, Cr(VI), Ni, and Pb had adverse effects on pediatric respiratory health during the study period. New strategies are required to decrease the production of PM2.5 and PM2.5-bound metals by motor vehicles and to reduce levels of street dust to reduce children's exposure to these pollutants and thereby increase child health.

Electron beam irradiation grafting of metal-organic frameworks onto cotton to prepare antimicrobial textiles.

Textiles modified with antimicrobial nanomaterials have excellent comprehensive performance. However, the shedding of nanoparticles often occurs in actual use. This not only reduces the service life of antimicrobial textiles, but also causes potential harm. Here, we report a new method to covalently immobilize a zinc-imidazolate MOF (ZIF-8) onto cotton fabric by electron beam irradiation to prepare antimicrobial textiles with excellent durability. A series of characterization analysis showed the electron beam irradiation did not damage the structure of the ZIF-8 nanoparticles and the particles were successfully introduced onto cotton fibers via poly hydroxyethyl acrylate (PHEA). The modified cotton fabric exhibited >99% inhibition of Escherichia coli, Staphylococcus aureus and Candida albicans. The results of dry cleaning and rub resistance tests showed that the prepared antimicrobial cotton fabric had significant durability which was attributed to the strong covalent binding between the MOF and textile.

Development and Internal Validation of a Prediction Model for Difficult Laryngoscopy Using Ultrasound-Derived Factor in Comatose Patients.

OBJECTIVES: The distance from skin to the hyoid bone (DSHB) and skin to the anterior commissure of vocal cords (DSAC) are reliable parameters for pre-operative airway ultrasound assessment in awake patients and can be assessed in comatose patients. This study aimed to inspect its feasibility and accuracy in predicting difficult laryngoscopy for comatose patients. METHODS: A prospective cohort study included patients with a Glasgow Coma Scale (GCS) of ≤8 who underwent emergency tracheal intubation between November 2019 and August 2020. The outcome was difficult laryngoscopy and classified according to the Cormack-Lehane grading. RESULTS: A total of 151 patients were included in the study. Fifty-two (34.4%) patients were categorized as having difficult laryngoscopy. The DSHB add DSAC (hereinafter referred to as the "DSBAC") was superior to either parameter alone in the predictive performance, and the optimal cut-off value was 1.90. To optimize the predictive value, DSBAC (adjusted odds ratio [OR]: 7.76; 95% confidence interval [CI]: 2.88-20.94; P < .001), GCS (adjusted OR: 1.39; 95% CI: 3.93-26.28; P = .039), mandibular retraction (adjusted OR: 8.20; 95% CI: 1.92-35.09; P = .005) and edentulous (adjusted OR: 4.23; 95% CI: 1.40-12.80; P = .011) were included in a multivariable model and constructed a nomogram. Discrimination and calibration statistics were satisfactory, with C-index above 0.80 from both model development and internal validation. CONCLUSIONS: Ultrasound-derived factor, DSBAC, can be easily assessed and help predict difficult laryngoscopy among comatose patients. A simple nomogram including only four clinical items exhibited excellent discrimination performance and was useful when comatose patients underwent emergency tracheal intubation.

The predictive effect of direct-indirect bilirubin ratio on clinical events in acute coronary syndrome: results from an observational cohort study in north China.

BACKGROUND: Patients with extremely high-risk ASCVD usually suffered poor prognosis, bilirubin is considered closely related to cardiovascular outcomes. However, there is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of the DIBIL ratio in patients with extremely high-risk ASCVD. METHODS: 10,260 consecutive patients with extremely high-risk ASCVD were enrolled in this study. All patients were divided into three groups according to their DIBIL ratio. The incidence of MACCEs was recorded, and in a competing risk regression, the incidence of MACCEs and their subgroups were recorded. The direct-indirect bilirubin ratio (DIBIL ratio) was calculated by the direct bilirubin (umol/L)/indirect bilirubin (umol/L) ratio, all laboratory values were obtained from the first fasting blood samples during hospitalization. RESULTS: The area under the ROC curve of the DIBIL ratio to predict the occurrence of all-cause death was 0.668, the cut-off value of which is 0.275. Competing risk regression indicated that DIBIL ratio was positively correlated with all-cause death [1.829 (1.405-2.381), p < 0.001], CV death [1.600 (1.103, 2.321), p = 0.013]. The addition of DIBIL ratio to a baseline risk model had an incremental effect on the predictive value for all-cause death [IDI 0.004(0, 0.010), p < 0.001; C-index 0.805(0.783-0.827), p < 0.001]. CONCLUSION: The DIBIL ratio was an excellent tool to predict poor prognosis, suggesting that this index may be developed as a biomarker for risk stratification and prognosis in extremely ASCVD patients.

Association of haemoglobin glycation index with outcomes in patients with acute coronary syndrome: results from an observational cohort study in China.

BACKGROUND: The hemoglobin glycation index (HGI) is the difference between measured and estimated glycation of hemoglobin. However, there is limited evidence to investigate the HGI and the clinical outcomes of acute coronary syndrome patients. This study aimed to evaluate the association between HGI and the clinical outcomes of acute coronary syndrome (ACS) in a China cohort. METHOD: This single-center retrospective study was carried out in the Cardiovascular Center of Beijing Friendship Hospital, a total of 11004 consecutive patients with ACS from Dec 2012-Dec 2020 were enrolled in this study. Patients were divided into quintiles according to their HGI levels. The incidence of major adverse cardiac and cerebrovascular events (MACCEs) was recorded. RESULT: HGI were divided into five quintiles quintiles: -0.906 (-7.188, -0.663), -0.491 (-0.663, -0.343), -0.196 (-0.342, -0.039), 0.170 (-0.039, 0.485), and 1.156 (0.485, 7.875), respectively. Competing risk regression revealed that HGI was positively related to all-cause death, CV death, and composite MACCEs. Multivariate Cox proportional hazards regression analysis indicated that hypertension (HR:1.109, P = 0.013), previous stroke (HR:1.208, P < 0.001), past PCI (HR: 1.268, P < 0.001), age (HR: 1.011, P < 0.001), BMI (HR: 0.987, P = 0.012), heart rate (HR: 1.004, P = 0.001), NSTEMI (HR: 1.205, P < 0.001), WBC (HR: 1.020, P = 0.008), eGFR (HR: 0.993, P < 0.001), HDL-C (HR: 0.809, P = 0.002), LVEF (HR:0.240, P < 0.001), LM/three-vessel or proximal LAD involved (HR: 1.208 P < 0.001; HR:0.914, P = 0.019, respectively), and antiplatelet agents during hospitalization (HR:0.806, P = 0.020) independently predicted the incidence of MACCEs in ACS patients. Restricted cubic spline indicated a U-shaped association between the HGI and risk of MACCEs. CONCLUSION: Both low HGI and high HGI was associated with an increased risk of adverse outcomes in patients with acute coronary syndrome, compared with moderate HGI.

Establishment of prognostic model for postoperative patients with metaplastic breast cancer: Based on a retrospective large data analysis and Chinese multicenter study.

Purpose: Models for predicting postoperative overall survival of patients with metaplastic breast cancer have not yet been discovered. The purpose of this study is to establish a model for predicting postoperative overall survival of metaplastic breast cancer patients. Methods: Patients in the Surveillance, Epidemiology, and End Results database diagnosed with MBC from 2010 to 2015 were selected and randomized into a SEER training cohort and an internal validation cohort. We identified independent prognostic factors after MBC surgery based on multivariate Cox regression analysis to construct nomograms. The discriminative and predictive power of the nomogram was assessed using Harrell's consistency index (C-index) and calibration plots. The decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model. We verify the performance of the prediction model with a Chinese multi-center data set. Results: Multifactorial analysis showed that age at diagnosis, T stage, N stage, M stage, tumor size, radiotherapy, and chemotherapy were important prognostic factors affecting OS. The C-index of nomogram was higher than the eighth edition of the AJCC TNM grading system in the SEER training set and validation set. The calibration chart showed that the survival rate predicted by the nomogram is close to the actual survival rate. It has also been verified in the SEER internal verification set and the Chinese multi-center data set. Conclusion: The prognostic model can accurately predict the post-surgical OS rate of patients with MBC and can provide a reference for doctors and patients to establish treatment plans.

The Role of Mitochondria in Metabolic Syndrome-Associated Cardiomyopathy.

With the rapid development of society, the incidence of metabolic syndrome (MS) is increasing rapidly. Evidence indicated that patients diagnosed with MS usually suffered from cardiomyopathy, called metabolic syndrome-associated cardiomyopathy (MSC). The clinical characteristics of MSC included cardiac hypertrophy and diastolic dysfunction, followed by heart failure. Despite many studies on this topic, the detailed mechanisms are not clear yet. As the center of cellular metabolism, mitochondria are crucial for maintaining heart function, while mitochondria dysfunction plays a vital role through mechanisms such as mitochondrial energy deprivation, calcium disorder, and ROS (reactive oxygen species) imbalance during the development of MSC. Accordingly, in this review, we will summarize the characteristics of MSC and especially focus on the mechanisms related to mitochondria. In addition, we will update new therapeutic strategies in this field.

Simulation of Land-Use Spatiotemporal Changes under Ecological Quality Constraints: The Case of the Wuhan Urban Agglomeration Area, China, over 2020-2030.

Human activities coupled with land-use change pose a threat to the regional ecological environment. Therefore, it is essential to determine the future land-use structure and spatial layout for ecological protection and sustainable development. Land use simulations based on traditional scenarios do not fully consider ecological protection, leading to urban sprawl. Timely and dynamic monitoring of ecological status and change is vital to managing and protecting urban ecology and sustainable development. Remote sensing indices, including greenness, humidity, dryness, and heat, are calculated annually. This method compensates for data loss and difficulty in stitching remote sensing ecological indices over large-scale areas and long time-series. Herein, a framework is developed by integrating the four above-mentioned indices for a rapid, large-scale prediction of land use/cover that incorporates the protection of high ecological quality zone (HEQZ) land. The Google Earth Engine (GEE) platform is used to build a comprehensive HEQZ map of the Wuhan Urban Agglomeration Area (WUAA). Two scenarios are considered: Ecological protection (EP) based on HEQZ and natural growth (NG) without spatial ecological constraints. Land use/cover in the WUAA is predicted over 2020-2030, using the patch-generating land use simulation (PLUS) model. The results show that: (1) the HEQZ area covers 21,456 km2, accounting for 24% of the WUAA, and is mainly distributed in the Xianning, Huangshi, and Xiantao regions. Construction land has the highest growth rate (5.2%) under the NG scenario. The cropland area decreases by 3.2%, followed by woodlands (0.62%). (2) By delineating the HEQZ, woodlands, rivers, lakes, and wetlands are well protected; construction land displays a downward trend based on the EP scenario with the HEQZ, and the simulated construction land in 2030 is located outside the HEQZ. (3) Image processing based on GEE cloud computing can ameliorate the difficulties of remote sensing data (i.e., missing data, cloudiness, chromatic aberration, and time inconsistency). The results of this study can provide essential scientific guidance for territorial spatial planning under the premise of ecological security.

Evaluation of Sampson equation for LDL-C in acute coronary syndrome patients: a Chinese population-based cohort study.

OBJECTIVE: Low-density lipoprotein cholesterol (LDL-C) is an important cardiovascular disease marker that is used to estimate the risk of acute coronary syndrome in patients. The Sampson equation is an accurate LDL-C equation, but its application in Chinese patients is unclear. METHODS: This study enrolled 12,989 consecutive Chinese patients with the acute coronary syndrome (ACS), LDL-C levels were determined by direct standard method and two indirect equations (Friedewald and Sampson). The detection accuracy and consistency of these two equations were compared in patients classified by triglyceride (TG). In addition, the efficiency of the Sampson equation was also evaluated in patients with different comorbidities. RESULTS: Patients were divided into six groups according to TG level, and indicated that the Sampson formula was more accurate than the Friedewald formula in all TG spectrums (P < 0.001). The Friedewald formula may underestimate the risk in patients with TG > 400 mg/dL, especially in TG > 800 mg/dL group (r: 0.931 vs. 0.948, 0.666 vs. 0.898, respectively). Compared with the Friedewald equation, the Sampson equation showed more advantages in female, age ≥ 65, body index mass (BMI) < 25, non-smoker, and non-diabetes (0.954 vs. 0.937, 0.956 vs. 0.934, 0.951 vs. 0.939, 0.951 vs. 0.936, and 0.947 vs. 0.938, respectively) than those in male, age < 65, BMI ≥ 25, smoker, and diabetes. CONCLUSIONS: Compared with the Friedewald equation, the Sampson equation is more accurate for LDL-C evaluation in Chinese patients diagnosed with ACS, especially in patients with hypertriglyceridemia even in those with TG > 800 mg/dL. Additionally, the Sampson equation demonstrates greater accuracy even in subgroups of various baseline characteristics and comorbidities.

Auxin concentration and xylem production of Pinus massoniana in a subtropical forest in south China.

Auxin is involved in various developmental processes of plants, including cell division in cambium and xylem differentiation. However, most studies linking auxin and xylem cell production are performed in environments with a strong seasonality (i.e., temperate and boreal climates). The temporal dynamics of auxin and cambial activity of subtropical trees remain basically unknown. In this study, we sampled four microcores weekly in three individuals of Chinese red pine (Pinus massoniana Lamb.) from February to December 2015-16 to compare xylem formation with auxin concentration in subtropical China. During the entire period of sampling, the number of cambial cells varied from 2 to 7, while the number of cells in the enlarging zone ranged from 1 to 4 and from 1 to 5 in the wall-thickening zone. In 2015, the average auxin concentration was 3.46 ng g-1, with 33 xylem cells being produced at the end of the year. In 2016, a lower auxin concentration (2.59 ng g-1) corresponded to a reduced annual xylem production (13.7 cells). No significant relationship between auxin concentration and number of xylem cells in differentiation was found at the weekly scale. Unlike in boreal and temperate forests, the lack of wood formation seasonality in subtropical forests makes it more difficult to reveal the relationship between auxin concentration and number of xylem cells in differentiation at the intra-annual scale. The frequent and repeated samplings might have reduced auxin concentration in the developing cambium and xylem, resulting in a lower xylem cell production.

Compound Optimization of Territorial Spatial Structure and Layout at the City Scale from "Production-Living-Ecological" Perspectives.

Land-use optimization, as an important resource-allocation method, can be defined as the process of allocating various activities to different geographic units. How to manage and control land expansion has become an urgent issue, leading a series of problems such as environmental damage and a sharp decrease in cultivated land, leading to unfavorable phenomena such as excessive urban expansion, occupation of cultivated land and important ecological spaces, and overheating of real estate development. Based on the land-use data of Wuhan city in 2020, a coupling MOP (Multi-Objective Programming) and FLUS (Future Land-Use Simulation) model was used to examine the national spatial structure and the optimization of the spatial layout. Our results showed that (1) in terms of quantitative optimal allocation, the ecological space and urban space increased, while the agricultural space greatly decreased under the three development scenarios. (2) In the simulation of spatial layout, the urban space mainly expanded vertically in the north-south direction. In the ecological space scenario, the ecological space occupied part of the cultivated land in the northeast of the city, resulting in a high degree of landscape fragmentation, which is not conducive to large-scale agricultural management. However, under optimal comprehensive benefit, part of the fragmented ecological space in the western part of Wuhan was transformed into an agricultural space. (3) A combination of the MOP and FLUS models could effectively determine land-use structure and address spatial layout optimization problems and can project space in the future urban resource configuration mode. This finding can provide a reference for the optimization of the spatial structure and layout of similar cities.

New Insights Into the Role of Mitochondria Quality Control in Ischemic Heart Disease.

IHD is a significant cause of mortality and morbidity worldwide. In the acute phase, it's demonstrated as myocardial infarction and ischemia-reperfusion injury, while in the chronic stage, the ischemic heart is mainly characterised by adverse myocardial remodelling. Although interventions such as thrombolysis and percutaneous coronary intervention could reduce the death risk of these patients, the underlying cellular and molecular mechanisms need more exploration. Mitochondria are crucial to maintain the physiological function of the heart. During IHD, mitochondrial dysfunction results in the pathogenesis of ischemic heart disease. Ischemia drives mitochondrial damage not only due to energy deprivation, but also to other aspects such as mitochondrial dynamics, mitochondria-related inflammation, etc. Given the critical roles of mitochondrial quality control in the pathological process of ischemic heart disease, in this review, we will summarise the efforts in targeting mitochondria (such as mitophagy, mtROS, and mitochondria-related inflammation) on IHD. In addition, we will briefly revisit the emerging therapeutic targets in this field.

Pseudo-zwitterions self-assembled from polycation and anion clusters showing exceptional water-cleanable anti-crude-oil-adhesion property.

It is of great importance and practical value to develop a facile and operable surface treatment method of materials with excellent antipollution and antiadhesion property, but still a huge challenge. In this work, a series of pseudo-zwitterions are prepared from electrostatic assembly of cationic polyethyleneimine and anionic phosphonic clusters. These pseudo-zwitterionic assemblies provide a strong hydration through electrostatic interaction with water and in turn create a barrier against oil foulants, leading to a nearly zero crude oil adhesion force. The pseudo-zwitterions-decorated surfaces exhibit exceptional water-cleanable oil-repellent property, even when they are completely dried and without prehydration before fouled by crude oil. While using these pseudo-zwitterions-modified polymeric membranes for separating surfactant stabilized oil-in-water emulsion, less than 10% decline of permeating flux is observed throughout a 2-h continuous separation experiment, showing excellent emulsion separation ability and antipollution performance for high viscous oil.

Obatoclax, the pan-Bcl-2 inhibitor sensitizes hepatocellular carcinoma cells to promote the anti-tumor efficacy in combination with immune checkpoint blockade.

Bcl-2 family proteins play critical roles in regulating lymphocyte development and maintain homeostasis, and have also been proved to be involved in various cancer types development. However, the role of Bcl-2 in hepatocellular carcinoma (HCC) development has not been clearly studied. Here, we reported the pan-Bcl-2 inhibitor, obatoclax could directly inhibit HCC growth in vitro. We further demonstrated in murine HCC model that obatoclax also suppressed HCC development in vivo. We also proved that although obatoclax inhibited T cells expansion, it had no influence on T cells activation in vivo. Mechanism study revealed that obatoclax sensitized HCC cells to T cell-mediated killing. Combination therapy of obatoclax with anti-PD-1 antibody synergistically suppressed HCC development and prolonged the survival rate of tumor-bearing mice. The combination therapy promoted T cells activation and effector cytokines expression both in spleen and tumor. In summary, our results proved that obatoclax sensitized HCC cells to T cell -mediated killing. Combination of obatoclax with immune checkpoint blockade served as a promising therapeutic strategy for HCC treatment.

Effect of family history of atrial fibrillation on recurrence after atrial fibrillation ablation: A report from the Chinese Atrial Fibrillation Registry Study.

BACKGROUND: To evaluate the impact of family history of atrial fibrillation (FAF) on postablation atrial tachyarrhythmia (AT) recurrence. METHODS: All the 8198 patients undergoing initial AF ablation registered in the Chinese Atrial Fibrillation Registry study were analyzed. FAF was defined as having first-degree relatives diagnosed as AF at age 65 years or younger, and before the time the case in this study was diagnosed. Cox proportional hazards models were used to evaluate the impact of FAF on postablation AT recurrence. Age, sex, body mass index, AF type, history of congestive heart failure, hypertension, diabetes mellitus, prior stroke/transient ischemic attack/systemic embolism, vascular diseases, use of contact force-sensing catheter, and completion of high school were adjusted. The definition of AT recurrence was any documented AF, atrial flutter, or AT lasting more than or equal to 30 s after 3 months blanking period. RESULTS: After a mean follow-up of 26.2 ± 19.6 months, 318 out of the 645 patients (49.3%) with FAF and 3339 out of the 7553 patients (44.2%) without FAF experienced AT recurrence, corresponding to annual recurrence rates of 22.8% and 20.2%, respectively. Patients with FAF had a significant higher risk of AT recurrence (adjusted hazard ratio 1.129, 95% confidence interval 1.005-1.267) in multivariable analysis. Moreover, FAF had a significant higher impact on AT recurrence in the subgroup of patients diagnosed with AF at age 50 years or younger (p for interaction = .036). CONCLUSION: FAF is a risk factor for postablation AT recurrence. This is especially true in those with AF diagnosed at 50 years or younger.

Radiation Induced Surface Modification of Nanoparticles and their Dispersion in the Polymer Matrix.

Polymer grafted inorganic nanoparticles attract significant attention, but pose challenges because of the complexity. In this work, a facile strategy to the graft polymer onto the surface of nanoparticles have been introduced. The vinyl functionalized SiO2 nanoparticles (NPs) were first prepared by the surface modification of the unmodified SiO2 using γ-methacryloxy propyl-trimethoxylsilane. The NPs were then mixed with polyvinylidene fluoride (PVDF), which was followed by the Co-60 Gamma radiation at room temperature. PVDF molecular chains were chemically grafted onto the surface of SiO2 nanoparticles by the linking of the double bond on the NPs. The graft ratio of PVDF on SiO2 NPs surface can be precisely controlled by adjusting the absorbed dose and reactant feed ratio (maximum graft ratio was 31.3 wt%). The strategy is simple and it should be applied to the surface modification of many other nanoparticles. The prepared PVDF-grafted SiO2 NPs were then dispersed in the PVDF matrix to make the nanocomposites. It was found that the modified NPs can be precisely dispersed into the PVDF matrix, as compared with pristine silica. The filling content of modifications SiO2 NPs on the PVDF nanocomposites is almost doubled than the pristine SiO2 counterpart. Accordingly, the mechanical property of the nanocomposites is significantly improved.