Association of cumulative resting heart rate exposure with rapid renal function decline: a prospective cohort study with 27,564 older adults.

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS: The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Engineering nanoparticle toolkits for mRNA delivery.

The concept of using mRNA to produce its own medicine in situ in the body makes it an ideal drug candidate, holding great potential to revolutionize the way we approach medicine. The unique characteristics of mRNA, as well as its customizable biomedical functions, call for the rational design of delivery systems to protect and transport mRNA molecules. In this review, a nanoparticle toolkit is presented for the development of mRNA-based therapeutics from a drug delivery perspective. Nano-delivery systems derived from either natural systems or chemical synthesis, in the nature of organic or inorganic materials, are summarised. Delivery strategies in controlling the tissue targeting and mRNA release, as well as the role of nanoparticles in building and boosting the activity of mRNA drugs, have also been introduced. In the end, our insights into the clinical and translational development of mRNA nano-drugs are presented.

Bioengineered materials with selective antimicrobial toxicity in biomedicine.

Fungi and bacteria afflict humans with innumerous pathogen-related infections and ailments. Most of the commonly employed microbicidal agents target commensal and pathogenic microorganisms without discrimination. To distinguish and fight the pathogenic species out of the microflora, novel antimicrobials have been developed that selectively target specific bacteria and fungi. The cell wall features and antimicrobial mechanisms that these microorganisms involved in are highlighted in the present review. This is followed by reviewing the design of antimicrobials that selectively combat a specific community of microbes including Gram-positive and Gram-negative bacterial strains as well as fungi. Finally, recent advances in the antimicrobial immunomodulation strategy that enables treating microorganism infections with high specificity are reviewed. These basic tenets will enable the avid reader to design novel approaches and compounds for antibacterial and antifungal applications.

Tailoring head-tail mesoporous silica nanoparticles for enhanced gene transfection.

Plasmid DNA (pDNA) delivery has attracted extensive research interest due to its great potential in gene therapy. The design of efficient nano-vectors to promote cellular delivery and transfection of gene molecules is the key to success. Compared to conventional nanocarriers with spherical geometry, asymmetric nanoparticles have been well documented showing enhanced cellular uptake and drug delivery capability. However, the impact of asymmetric nanostructures on pDNA binding and following intracellular delivery performance has been less reported. Herein, asymmetric head-tail mesoporous silica nanoparticles (HTMSNs) with tailored tail lengths were synthesized and employed as nano-vectors for pDNA delivery. The nanostructures of HTMSNs were carefully characterized by electron tomography. The pDNA binding, cellular uptake and gene transfection capabilities of engineered asymmetric nanoparticles were compared with symmetric dendritic mesoporous silica nanoparticles (DMSNs). The results showed that the asymmetric morphology of nanoparticles promoted pDNA binding and cell internalization, where HTMSNs-66 with a specific tail length of 66 nm achieved the highest transfection efficiency. This study reveals the impact of asymmetric nanostructure on DNA interaction, and provides guidance in future designs of non-viral nano-vectors for efficient gene delivery.

Co-Delivery of Nano-Silver and Vancomycin via Silica Nanopollens for Enhanced Antibacterial Functions.

Infectious diseases caused by bacteria have led to a great threat to public health. With the significant advances in nanotechnology in recent decades, nanomaterials have emerged as a powerful tool to boost antibacterial performance due to either intrinsic bactericidal properties or by enhancing the delivery efficiency of antibiotics for effective pathogen killing. Vancomycin, as one of the most widely employed antimicrobial peptides, has a potent bactericidal activity, but at the same time shows a limited bioavailability. Silver nanoparticles have also been extensively explored and were found to have a well-recognized antibacterial activity and limited resistance potential; however, how to prevent nanosized Ag particles from aggregation in biological conditions is challenging. In this study, we aimed to combine the advantages of both vancomycin and nano-Ag for enhanced bacterial killing, where both antibacterial agents were successfully loaded onto a silica nanoparticle with a pollen-like morphology. The morphology of nano-Ag-decorated silica nanopollens was characterized using transmission electron microscopy and elemental mapping through energy dispersive spectroscopy. Silver nanoparticles with a size of 10-25 nm were observed as well-distributed on the surface of silica nanoparticles of around 200 nm. The unique design of a spiky morphology of silica nano-carriers promoted the adhesion of nanoparticles towards bacterial surfaces to promote localized drug release for bacterial killing, where the bacterial damage was visualized through scanning electron microscopy. Enhanced bactericidal activity was demonstrated through this co-delivery of vancomycin and nano-Ag, decreasing the minimum inhibition concentration (MIC) towards E. coli and S. epidermidis down to 15 and 10 µg/mL. This study provides an efficient antimicrobial nano-strategy to address potential bacterial infections.

Asymmetric Silica Nanoparticles with Tailored Spiky Coverage Derived from Silica-Polymer Cooperative Assembly for Enhanced Hemocompatibility and Gene Delivery.

Asymmetric mesoporous silica nanoparticles (AMSNs) with one side featuring a spiky nanotopography, while the other side is smooth and solid, were synthesized via an ethylenediamine (EDA)-directed silica-polymer cooperative assembly approach. By simply varying the EDA amount (x), AMSNs-x samples with adjustable spiky surface coverage were obtained. It is demonstrated that a spiky coverage higher than 50% improved the hemocompatibility of AMSN-x, possibly due to the reduced contact area of the smooth side exposed to the red blood cell (RBC) membrane. Moreover, AMSNs-175 and AMSNs-200 with high spiky coverage enhanced their plasmid DNA (pDNA) loading and binding capability, as well as cellular uptake into HEK-293T cells, thus resulting in high transfection performance. The good hemocompatibility and high performance in pDNA delivery of AMSNs-x with high spiky coverage allow them to serve as promising nonviral vectors for potential applications in gene therapies and DNA vaccines.