Very few studies have examined sleep duration in relation to cancer incidence with the exception of breast cancer.
We assessed the associations between sleep duration and incidences of total and 18 ...site-specific cancers in the NIH-AARP Health and Diet Study cohort, with 173,327 men and 123,858 women aged 51-72 years at baseline. Self-reported sleep duration categories were assessed via questionnaire. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), using 7-8 hours/night as the reference.
We observed a significantly increased risk of stomach cancer among male short sleepers (multivariable HR5-6 vs. 7-8 hours = 1.29; 95%CI: 1.05, 1.59; Ptrend = 0.03). We also observed suggestive associations in either short or long sleepers, which did not reach overall significance (Ptrend >0.05), including increased risks in male short sleepers for cancers of head and neck (HR<5vs.7-8 hours = 1.39; 95%CI:1.00-1.95), bladder (HR5-6vs.7-8 hours = 1.10; 95%CI:1.00-1.20), thyroid (HR<5 vs. 7-8 hours = 2.30; 95%CI:1.06, 5.02), Non-Hodgkin Lymphoma (NHL) (HR5-6vs.7-8 hours = 1.17; 95%CI:1.02-1.33), and myeloma (HR<5vs.7-8 hours = 2.06; 95%CI:1.20-3.51). In women, the suggestive associations include a decreased total cancer risk (HR<5vs.7-8 hours = 0.9; 95%CI:0.83-0.99) and breast cancer risk (HR<5vs.7-8 hours = 0.84; 95%CI:0.71-0.98) among short sleepers. A decreased ovarian cancer risk (HR≥ 9 vs. 7-8 hours = 0.50; 95%CI:0.26-0.97) and an increased NHL risk (HR≥ 9 vs. 7-8 hours = 1.45; 95%CI:1.00-2.11) were observed among long sleepers.
In an older population, we observed an increased stomach cancer risk in male short sleepers and suggestive associations with short or long sleep duration for many cancer risks in both genders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide‐bond‐containing organosilica moieties into the framework of silica to fabricate biodegradable ...mesoporous silica nanoparticles (MSNs) with oxidative and redox dual‐responsiveness is reported. These diselenide‐bridged MSNs can encapsulate cytotoxic RNase A into the 8–10 nm internal pores via electrostatic interaction and release the payload via a matrix‐degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer‐cell‐derived membrane fragments, these bioinspired RNase A‐loaded MSNs exhibit homologous targeting and immune‐invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti‐cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell‐membrane‐coated, dual‐responsive degradable MSNs represent a promising platform for the delivery of bio‐macromolecules such as protein and nucleic acid therapeutics.
Diselenide‐bond‐containing organosilica moieties are introduced into the framework of mesoporous silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with an oxidative and redox dual‐responsive degradable feature. After surface cloaking with cancer‐cell‐derived membrane fragments, these bioinspired RNase‐A‐loaded MSNs exhibit homologous targeting and immune escape abilities, leading to efficient in vitro and in vivo anti‐cancer performance along with low toxicity.
Ignition experiments have shown an anomalous susceptibility to hydrodynamic instability growth. To help understand these results, the first hydrodynamic instability growth measurements in indirectly ...driven implosions on the National Ignition Facility were performed at ignition conditions with peak radiation temperatures up to ∼300 eV. Plastic capsules with two-dimensional preimposed, sinusoidal outer surface modulations of initial wavelengths of 240 (corresponding to a Legendre mode number of 30), 120 (mode 60), and 80 μm (mode 90) were imploded by using actual low-adiabat ignition laser pulses. The measured growth was in excellent agreement, validating 2D hydra simulations for the most dangerous modes in the acceleration phase. These results reinforce confidence in the predictive capability of calculations that are paramount to illuminating the path toward ignition.
Inflammation is ubiquitous in the body, triggering desirable immune response to defend against dangerous signals or instigating undesirable damage to cells and tissues to cause disease. Nanomedicine ...holds exciting potential in modulating inflammation. In particular, cell membranes derived from cells involved in the inflammatory process may be used to coat nanotherapeutics for effective targeted delivery to inflammatory tissues. Herein, the recent progress of rationally engineering cell membrane‐based nanotherapeutics for inflammation therapy is highlighted, and the challenges and opportunities presented in realizing the full potential of cell‐membrane coating in targeting and manipulating the inflammatory microenvironment are discussed.
Recent advances of rationally engineering cell membrane‐based nanotherapeutics for inflammation therapy are summarized and the state‐of‐the‐art cell membrane engineering, extraction, and cloaking technologies are introduced. The challenges and opportunities of such bioinspired nanomedicine allow for the realization of the full potential of cell‐membrane coating in targeting and manipulating the inflammatory microenvironment.
Aptamer nanomedicine, including therapeutic aptamers and aptamer nanocomplexes, is beginning to fulfill its potential in both clinical trials and preclinical studies. Especially in oncology, aptamer ...nanomedicine may perform better than conventional or antibody-based chemotherapeutics due to specificity compared to the former and stability compared to the latter. Many proof-of-concept studies on applying aptamers to drug delivery, gene therapy, and cancer imaging have shown promising efficacy and impressive safety in vivo toward translation. Yet, there remains ample room for improvement and critical barriers to be addressed. In this review, we will first introduce the recent progress in clinical trials of aptamer nanomedicine, followed by a discussion of the barriers at the design and in vivo application stages. We will then highlight recent advances and engineering strategies proposed to tackle these barriers. Aptamer cancer nanomedicine has the potential to address one of the most important healthcare issues of the society.
Effective and safe delivery of the CRISPR/Cas9 gene-editing elements remains a challenge. Here we report the development of PEGylated nanoparticles (named P-HNPs) based on the cationic α-helical ...polypeptide poly(γ-4-((2-(piperidin-1-yl)ethyl)aminomethyl)benzyl-L-glutamate) for the delivery of Cas9 expression plasmid and sgRNA to various cell types and gene-editing scenarios. The cell-penetrating α-helical polypeptide enhanced cellular uptake and promoted escape of pCas9 and/or sgRNA from the endosome and transport into the nucleus. The colloidally stable P-HNPs achieved a Cas9 transfection efficiency up to 60% and sgRNA uptake efficiency of 67.4%, representing an improvement over existing polycation-based gene delivery systems. After performing single or multiplex gene editing with an efficiency up to 47.3% in vitro, we demonstrated that P-HNPs delivering Cas9 plasmid/sgRNA targeting the polo-like kinase 1 (Plk1) gene achieved 35% gene deletion in HeLa tumor tissue to reduce the Plk1 protein level by 66.7%, thereby suppressing the tumor growth by >71% and prolonging the animal survival rate to 60% within 60 days. Capable of delivering Cas9 plasmids to various cell types to achieve multiplex gene knock-out, gene knock-in, and gene activation in vitro and in vivo, the P-HNP system offers a versatile gene-editing platform for biological research and therapeutic applications.
Localized optical resonances in metallic nanostructures have been increasingly used in color printing, demonstrating unprecedented resolution but limited in color gamut. Here, we introduce a new ...nanostructure design, which broadens the gamut while retaining print resolution. Instead of metals, silicon nanostructures that exhibit localized magnetic and electric dipole resonances were fabricated on a silicon substrate coated with a Si3N4 index matching layer. Index matching allows a suppression of substrate effects, thus enabling Kerker’s conditions to be met, that is, sharpened transitions in the reflectance spectra leading to saturated colors. This nanostructure design achieves a color gamut superior to sRGB, and is compatible with CMOS processes. The presented design could enable compact high-resolution color displays and filters, and the use of a Si3N4 antireflection coating can be readily extended to designs with nanostructures fabricated using other high-index materials.
Human papillomavirus 16 (HPV16) species group (alpha-9) of the Alphapapillomavirus genus contains HPV16, HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. These HPVs account for 75% of invasive cervical ...cancers worldwide. Viral variants of these HPVs differ in evolutionary history and pathogenicity. Moreover, a comprehensive nomenclature system for HPV variants is lacking, limiting comparisons between studies.
DNA from cervical samples previously characterized for HPV type were obtained from multiple geographic regions to screen for novel variants. The complete 8 kb genomes of 120 variants representing the major and minor lineages of the HPV16-related alpha-9 HPV types were sequenced to capture maximum viral heterogeneity. Viral evolution was characterized by constructing phylogenic trees based on complete genomes using multiple algorithms. Maximal and viral region specific divergence was calculated by global and pairwise alignments. Variant lineages were classified and named using an alphanumeric system; the prototype genome was assigned to the A lineage for all types.
The range of genome-genome sequence heterogeneity varied from 0.6% for HPV35 to 2.2% for HPV52 and included 1.4% for HPV31, 1.1% for HPV33, 1.7% for HPV58 and 1.1% for HPV67. Nucleotide differences of approximately 1.0% - 10.0% and 0.5%-1.0% of the complete genomes were used to define variant lineages and sublineages, respectively. Each gene/region differs in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1) /noncoding region 2 (NCR2) >upstream regulatory region (URR)> E6/E7 > E2/L2 > E1/L1.
These data define maximum viral genomic heterogeneity of HPV16-related alpha-9 HPV variants. The proposed nomenclature system facilitates the comparison of variants across epidemiological studies. Sequence diversity and phylogenies of this clinically important group of HPVs provides the basis for further studies of discrete viral evolution, epidemiology, pathogenesis and preventative/therapeutic interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent advances in CRISPR present attractive genome‐editing toolsets for therapeutic strategies at the genetic level. Here, a liposome‐coated mesoporous silica nanoparticle (lipoMSN) is reported as ...an effective CRISPR delivery system for multiplex gene‐editing in the liver. The MSN provides efficient loading of Cas9 plasmid as well as Cas9 protein/guide RNA ribonucleoprotein complex (RNP), while liposome‐coating offers improved serum stability and enhanced cell uptake. Hypothesizing that loss‐of‐function mutation in the lipid‐metabolism‐related genes pcsk9, apoc3, and angptl3 would improve cardiovascular health by lowering blood cholesterol and triglycerides, the lipoMSN is used to deliver a combination of RNPs targeting these genes. When targeting a single gene, the lipoMSN achieved a 54% gene‐editing efficiency, besting the state‐of‐art Lipofectamine CRISPRMax. For multiplexing, lipoMSN maintained significant gene‐editing at each gene target despite reduced dosage of target‐specific RNP. By delivering combinations of targeting RNPs in the same nanoparticle, synergistic effects on lipid metabolism are observed in vitro and vivo. These effects, such as a 50% decrease in serum cholesterol after 4 weeks of post‐treatment with lipoMSN carrying both pcsk9 and angptl3‐targeted RNPs, could not be reached with a single gene‐editing approach. Taken together, this lipoMSN represents a versatile platform for the development of efficient, combinatorial gene‐editing therapeutics.
A liposome‐coated mesoporous silica nanoparticle enables multiplex gene editing to understand potential therapeutic targets in liver lipid metabolism. Using this novel nonviral platform to deliver CRISPR/Cas9 ribonucleoprotein, gene editing is demonstrated at three potential therapeutic targets (pcsk9, apoc3, angptl3) for cardioprotection in vitro and in vivo.
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