DNA Self-Assembly of Targeted Near-Infrared-Responsive Gold Nanoparticles for Cancer Thermo-Chemotherapy

Targeted Cancer Therapy: Inspired by the ability of DNA hybridization, a targeted near-infrared (NIR) light-responsive delivery system has been developed through simple DNA self-assembly (PEG=polyethylene glycol). This DNA-based platform shows the ability of releasing therapeutics upon near-infrared irradiation, and remarkable targeted thermo- and chemotherapeutic efficacy in vitro and in vivo

Prognostic and therapeutic significance of microbial cell-free DNA in plasma of people with acutely decompensated cirrhosis

BACKGROUND AND AIMS: Although the effect of bacterial infection on cirrhosis has been well-described, the effect of non-hepatotropic virus (NHV) infection is unknown. This study evaluated the genome fragments of circulating microorganisms using metagenomic next-generation sequencing (mNGS) in cirrhosis patients with acute decompensation (AD), focusing on NHVs and related the findings to clinical outcomes. METHODS: Plasma mNGS was performed in 129 cirrhosis patients with AD in study cohort. Ten healthy volunteers and 20, 39, and 81 patients with stable cirrhosis, severe sepsis and hematological malignancies, respectively, were enrolled as controls. Validation assays for human cytomegalovirus (CMV) reactivation in a validation cohort (n = 58) were performed and exploratory treatment instituted. RESULTS: In study cohort, 188 microorganisms were detected in 74.4% (96/129) patients, including viruses (58.0%), bacteria (34.1%), fungi (7.4%) and chlamydia (0.5%). Patients with AD had an NHV signature, and CMV was the most frequent NHV, which correlated with the clinical effect of empirical antibiotic treatment, progression to acute-on-chronic liver failure (ACLF), and 90-day mortality. The NHV signature in ACLF patients was similar to patients with sepsis and hematological malignancies. The treatable NHV, CMV was detected in 24.1% (14/58) patients in the validation cohort. Of the 14 cases with detectable CMV by mNGS, 9 were further validated by DNA RT-PCR or pp65 antigenemia testing. Three patients with CMV reactivation received ganciclovir therapy in exploratory manner with clinical resolutions. CONCLUSIONS: The results of this study suggests that NHVs may have a pathogenic role in complicating the course of AD. Further validation is needed to define whether this should be incorporated in the routine management of AD patients. IMPACT AND IMPLICATIONS: ●Cirrhosis patients with acute decompensation have a non-hepatotropic virus (NHV) signature, which is similar to that in sepsis and hematological malignancies patients. ●The detected viral signature had clinical correlates, including clinical efficacy of empirical antibiotic treatment, progression to acute-on-chronic liver failure and short-term mortality. ●The treatable NHV, CMV reactivation may be involved in the clinical outcomes of decompensated cirrhosis. ●Routine screening for NHVs, especially CMV, may be useful for the management of patients with acutely decompensated cirrhosis

Biomimetic Nanosilica-Collagen Scaffolds for In Situ Bone Regeneration: Toward a Cell-Free, One-Step Surgery.

Current approaches to fabrication of nSC composites for bone tissue engineering (BTE) have limited capacity to achieve uniform surface functionalization while replicating the complex architecture and bioactivity of native bone, compromising application of these nanocomposites for in situ bone regeneration. A robust biosilicification strategy is reported to impart a uniform and stable osteoinductive surface to porous collagen scaffolds. The resultant nSC composites possess a native-bone-like porous structure and a nanosilica coating. The osteoinductivity of the nSC scaffolds is strongly dependent on the surface roughness and silicon content in the silica coating. Notably, without the use of exogenous cells and growth factors (GFs), the nSC scaffolds induce successful repair of a critical-sized calvarium defect in a rabbit model. It is revealed that topographic and chemical cues presented by nSC scaffolds could synergistically activate multiple signaling pathways related to mesenchymal stem cell recruitment and bone regeneration. Thus, this facile surface biosilicification approach could be valuable by enabling production of BTE scaffolds with large sizes, complex porous structures, and varied osteoinductivity. The nanosilica-functionalized scaffolds can be implanted via a cell/GF-free, one-step surgery for in situ bone regeneration, thus demonstrating high potential for clinical translation in treatment of massive bone defects

Sciences for The 2.5-meter Wide Field Survey Telescope (WFST)

The Wide Field Survey Telescope (WFST) is a dedicated photometric survey facility under construction jointly by the University of Science and Technology of China and Purple Mountain Observatory. It is equipped with a primary mirror of 2.5m in diameter, an active optical system, and a mosaic CCD camera of 0.73 Gpix on the main focus plane to achieve high-quality imaging over a field of view of 6.5 square degrees. The installation of WFST in the Lenghu observing site is planned to happen in the summer of 2023, and the operation is scheduled to commence within three months afterward. WFST will scan the northern sky in four optical bands (u, g, r, and i) at cadences from hourly/daily to semi-weekly in the deep high-cadence survey (DHS) and the wide field survey (WFS) programs, respectively. WFS reaches a depth of 22.27, 23.32, 22.84, and 22.31 in AB magnitudes in a nominal 30-second exposure in the four bands during a photometric night, respectively, enabling us to search tremendous amount of transients in the low-z universe and systematically investigate the variability of Galactic and extragalactic objects. Intranight 90s exposures as deep as 23 and 24 mag in u and g bands via DHS provide a unique opportunity to facilitate explorations of energetic transients in demand for high sensitivity, including the electromagnetic counterparts of gravitational-wave events detected by the second/third-generation GW detectors, supernovae within a few hours of their explosions, tidal disruption events and luminous fast optical transients even beyond a redshift of 1. Meanwhile, the final 6-year co-added images, anticipated to reach g about 25.5 mag in WFS or even deeper by 1.5 mag in DHS, will be of significant value to general Galactic and extragalactic sciences. The highly uniform legacy surveys of WFST will also serve as an indispensable complement to those of LSST which monitors the southern sky.Comment: 46 pages, submitted to SCMP

DNA Self-Assembly of Targeted Near-Infrared-Responsive Gold Nanoparticles for Cancer Thermo-Chemotherapy

Targeted cancer therapy: Inspired by the ability of DNA hybridization, a targeted near-infrared (NIR) light-responsive delivery system has been developed through simple DNA self-assembly (see picture; PEG=polyethylene glycol). This DNA-based platform shows the ability of releasing therapeutics upon near-infrared irradiation, and remarkable targeted thermo- and chemotherapeutic efficacy in vitro and in vivo.National Institutes of Health (U.S.) (Grant CA151884)Prostate Cancer Foundation (Program in Cancer Nanotherapeutics