Long-term risks of cardiovascular death among older patients with major hematological malignancies: a population-based cohort study from SEER database.

BACKGROUND: The objective of this study was to identify the risk of cardiovascular disease (CVD)-related death in older patients with major hematological malignancies (HM). METHODS: This study included 103,102 older patients diagnosed with 7 major types of HM between 1975 and 2018 (median follow-up: 2.7 years) from the Surveillance, Epidemiology, and End Result (SEER) database. The proportion of deaths, Fine-Gray sub-distribution hazards regression model, standardized mortality ratios (SMR) and absolute excess risk (AER) were used to evaluate the risk of CVD-related death. RESULTS: For older patients with HM, CVD-related death ranked as the second leading cause of death, surpassed only by primary malignancy. Compared to the general older population, older patients with HM had higher SMR and AER of CVD-related deaths (SMR: 1.16-1.81; AER: 41.24-308.99), heart disease-related deaths (SMR: 1.19-1.90; AER: 39.23-274.69), and cerebrovascular dis-ease-related deaths (SMR: 0.99-1.66; AER: -0.35 -24.15). The proportion of deaths and cumulative mortality increased with the passage of survival time, especially in Hodgkin lymphoma patients with stage I/II and those aged ≥85 years with chronic lymphocytic leukemia, surpassing primary malignancy. The risk of CVD-related death varied among different HM types. CONCLUSIONS: For older patients with HM, long-term cardiovascular risk management needs to be focused on while addressing the primary malignancy. IMPACT: Our results emphasize the need to manage long-term cardiovascular risk in older patients with HM, especially in those identified as high-risk cases.

Droplet Evaporation Dynamics on Hydrophobic Network Surfaces.

Surface modification, such as hydrophobic network modification, is very promising technology to control droplet dynamics, heat transfer, and evaporation. However, fundamental mechanisms of how these chemically patterned surfaces affect the droplet evaporation dynamics and predictions of evaporation rates are still lacking. In the present work, we systematically investigated the full process of droplet evaporation dynamics on hydrophobic network surfaces and distinguished four different stages: constant contact line (CCL) stage, constant contact angle (CCA) stage, pattern-pinning (PP) stage, and moving contact line (MCL) stage. We further developed a general model considering the pinning and depinning forces to accurately predict the evaporation transition from PP to MCL stages (i.e., critical receding contact angle, θcr). As for the influence of the chemically patterned surface on the evaporation rate, a corrected contact line length was considered and combined with the well-known Rowan and Erbil's models. Finally, a general model was thus proposed and showed successful predictions for the evaporation durations of each stage.

Microfluidic production of nanoscale perfluorocarbon droplets as liquid contrast agents for ultrasound imaging.

Liquid perfluorocarbon (PFC) nanodroplets may have a better chance to extravasate through inter-endothelial gaps (400-800 nm) into tumor interstitium for extravascular imaging, which holds promise as an innovative strategy for imaging-guided drug delivery, early diagnosis of cancer and minimally invasive treatment of cancer. Currently available emulsion technologies still face challenges in reducing droplet sizes from the microscale to the nanoscale. To control size and ensure monodispersity of PFC nanodroplets, we developed a flame-shaped glass capillary and polydimethylsiloxane (PDMS) hybrid device that creates a concentric flow of the dispersed phase enclosed by the focusing continuous phase at the cross-junction. Through adjustment of the pressure applied, a stable tip-streaming mode can be obtained for PFC nanodroplet generation. Using this device, we synthesized various kinds of PFC nanodroplets as small as 200 nm in diameter with polydispersity index (PDI) <0.04. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were carried out for the characterization of the PFC nanodroplets. Finally, ultrasound imaging was conducted to demonstrate that the liquid PFC nanodroplets can be used for enhancing the ultrasound contrast upon vaporization.

Aggregation-Induced Emission Luminogen-Based Direct Visualization of Concentration Gradient Inside an Evaporating Binary Sessile Droplet.

In this study, the concentration gradient inside evaporating binary sessile droplets of 30, 50, and 60 vol % tetrahydrofuran (THF)/water mixtures was investigated. The 5 µL THF/water droplets were evaporated on a transparent hydrophobic substrate. This is the first demonstration of local concentration mapping within an evaporating binary droplet utilizing the aggregation-induced emission material. During the first two evaporation stages of the binary droplet, the local concentration can be directly visualized by the change of fluorescence emission intensity. Time-resolved average and local concentrations can be estimated by using the pre-established function of fluorescence intensity versus water volume fraction.

Multicomponent Droplet Evaporation on Chemical Micro-Patterned Surfaces.

The evaporation and dynamics of a multicomponent droplet on a heated chemical patterned surface were presented. Comparing to the evaporation process of a multicomponent droplet on a homogenous surface, it is found that the chemical patterned surface can not only enhance evaporation by elongating the contact line, but also change the evaporation process from three regimes for the homogenous surface including constant contact line (CCL) regime, constant contact angle (CCA) regime and mix mode (MM) to two regimes, i.e. constant contact line (CCL) and moving contact line (MCL) regimes. The mechanism of contact line stepwise movement in MCL regimes in the microscopic range is investigated in detail. In addition, an improved local force model on the contact line was employed for analyzing the critical receding contact angles on homogenous and patterned surfaces. The analysis results agree well for both surfaces, and confirm that the transition from CCL to MCL regimes indicated droplet composition changes from multicomponent to monocomponent, providing an important metric to predict and control the dynamic behavior and composition of a multicomponent droplet using a patterned surface.

Continuous-Flow Electrokinetic-Assisted Plasmapheresis by Using Three-Dimensional Microelectrodes Featuring Sidewall Undercuts.

We present a novel plasmapheresis device designed for a fully integrated point-of-care blood analysis microsystem. In the device, fluidic microchannels exhibit a characteristic cross-sectional profile arising from distinct three-dimensional (3D) microelectrodes featuring sidewall undercuts readily integrated through a single-mask process. The structure leverages mainly electrothermal convective rolls that efficiently manifest themselves in physiological fluids and yet have received inadequate attention for the application of plasmapheresis due to concerns over Joule heating. Using this device, we show that such convective rolls not only lead to plasma extraction at a high yield and purity but also deliver plasma at an acceptable quality with no evidence of hemolytic stress or protein denaturation. Specifically, plasma from 1.5 µL of whole blood diluted to 4% hematocrit in a high-conductivity buffer (1.5 S/m) is extracted in a continuous flow at a fraction of 70% by using a peak voltage of ±10 Vp applied at 650 kHz; the extracted plasma is nearly 99% pure, as shown by a rigorous assessment using flow cytometry. The plasmas obtained using this device and using conventional centrifugation and sedimentation are of comparable quality as revealed by absorbance and circular dichroism spectra despite thermal gradients; however, these gradients effectively drive electrothermal bulk flows, as assessed using the microparticle image velocity technique. The device achieves high target molecule recovery efficiency, delivering about 97% of the proteins detected in the plasma obtained using sedimentation. The utility of the extracted plasma is further validated based on the detection of prostate-specific antigen at clinically relevant levels.

A novel multifunctional poly(amidoamine) dendrimeric delivery system with superior encapsulation capacity for targeted delivery of the chemotherapy drug 10-hydroxycamptothecin.

With the aim of developing an efficient targeted delivery system for cancer therapy that overcomes drug leakage during circulation, we prepared a novel multifunctional dendrimeric carrier by integrating long hydrophobic C12 alkyl chains, poly(ethylene glycol) chains and c(RGDfK) ligands presented on the surface. This dendrimer was able to tightly encapsulate the hydrophobic anticancer drug 10-hydroxycamptothecin (10-HCPT) through simple complexation and selectively target the drug to cancer cells overexpressing integrin αvß3 through high affinity interactions. The complex has a high loading efficiency, with each molecule encapsulating approximately 20 drug molecules; high stability, without any detectable drug release during dialysis for three days; and high water solubility, achieving an approximately 600-fold increase over the water solubility of free 10-HCPT. This complex exhibited notably high cytotoxicity against 22RV1 cells overexpressing integrin αvß3 and a far lower cytotoxicity against MCF-7 cells, which express low levels of integrin αvß3. We expected encapsulated 10-HCPT to regain its anti-cancer activity following selective internalization of the complex into carcinoma cells via integrin receptor mediated endocytosis. As the drug remains inactive before internalization, this carrier has the ability to overcome problems associated with drug leakage in the circulation and off-target effects on normal tissues.

Systematic Analysis of the Functions of Lysine Acetylation in the Regulation of Tat Activity.

The Tat protein of HIV-1 has several well-known properties, such as nucleocytoplasmic trafficking, transactivation of transcription, interaction with tubulin, regulation of mitotic progression, and induction of apoptosis. Previous studies have identified a couple of lysine residues in Tat that are essential for its functions. In order to analyze the functions of all the lysine residues in Tat, we mutated them individually to alanine, glutamine, and arginine. Through systematic analysis of the lysine mutants, we discovered several previously unidentified characteristics of Tat. We found that lysine acetylation could modulate the subcellular localization of Tat, in addition to the regulation of its transactivation activity. Our data also revealed that lysine mutations had distinct effects on microtubule assembly and Tat binding to bromodomain proteins. By correlation analysis, we further found that the effects of Tat on apoptosis and mitotic progression were not entirely attributed to its effect on microtubule assembly. Our findings suggest that Tat may regulate diverse cellular activities through binding to different proteins and that the acetylation of distinct lysine residues in Tat may modulate its interaction with various partners.