Purpose: To analyze the prognostic factors and optimal response interval for stereotactic body radiotherapy (SBRT) in patients with lung oligometastases (OM) or oligoprogression (OP) from colorectal cancer (CRC).Method: Patients with lung OM or OP from CRC treated by SBRT at our hospital were included in this retrospective review. The local control (LC), response to SBRT in different evaluation interval and regional metastases (RM) was analyzed. The risk factor for LC and RM was calculated using the Kaplan-Meier method and compared using the Log-rank test. Multivariate analysis with a Cox proportional hazards model was used to test independent significance.Results: A total of 53 patients with 105 lung metastases lesions treated from 2012 to 2018 were involved in this retrospective study. The median biologically effective dose (BED) for these patients was 100 Gy (range: 75–131.2 Gy). Complete response (CR) increased from 27 (25.7%) to 46 (43.8%) lesions at 1.8 and 5.3 months following SBRT, and at the last follow-up, 52 (49.5%) lesions achieved CR. The median follow-up duration for all patients was 14 months (range: 5–63 months), and 1-year LC was 90.4%. During the follow-up, 10 lesions suffered local relapse after SBRT (9 of them occurred within 8 months after SBRT). The univariate analysis shows BED ≥ 100 Gy (P = 0.003) and gross tumor volume (GTV) < 1.6 cm3 (P = 0.011) were better predictors for 1-year LC. The patients with lung oligoprogression had higher 1-year RM when compared with patients with lung oligometastases (hazard ratio 2.78; 95% confidence interval [CI] 1.04–7.48, P = 0.042). Until the last follow up, 4 (7.5%) patients suffered grade 2 radiation pneumonitis, and no grade 3–4 toxicity was observed.Conclusions: SBRT provides favorable LC in CRC patients with lung OM or OP, and the GTV and BED can affect the LC. Radiology examinations nearly 5–6 months following SBRT appear to represent the final local effect of SBRT, and the patients with oligoprogression has higher RM.
Nucleic acid-based hydrogels that integrate intrinsic biological properties of nucleic acids and mechanical behavior of their advanced assemblies are appealing bioanalysis and biomedical studies for the development of new-generation smart biomaterials. It is inseparable from development and incorporation of novel structural and functional units. This review highlights different functional units of nucleic acids, polymers, and novel nanomaterials in the order of structures, properties, and functions, and their assembly strategies for the fabrication of nucleic acid-based hydrogels. Also, recent advances in the design of multifunctional and stimuli-responsive nucleic acid-based hydrogels in bioanalysis and biomedical science are discussed, focusing on the applications of customized hydrogels for emerging directions, including 3D cell cultivation and 3D bioprinting. Finally, the key challenge and future perspectives are outlined.
Sheep were one of the earliest domesticated animals. Both artificial and natural selection during domestication has resulted in remarkable changes in behavioral, physiological, and morphological phenotypes; however, the genetic mechanisms underpinning these changes remain unclear, particularly for indigenous Chinese sheep. In the present study, we performed pooled whole-genome resequencing of 338 sheep from five breeds representative of indigenous Chinese breeds and compared them to the wild ancestors of domestic sheep (Asian mouflon,
Ovis orientalis
) for detection of genome-wide selective sweeps. Comparative genomic analysis between domestic sheep and Asian mouflon showed that selected regions were enriched for genes involved in bone morphogenesis, growth regulation, and embryonic and neural development in domestic sheep. Moreover, we identified several vision-associated genes with funtional mutations, such as
PDE6B
(c.G2994C/p.A982P and c.C2284A/p.L762M mutations),
PANK2
, and
FOXC1/GMSD
in all five Chinese native breeds. Breed-specific selected regions were determined including genes such as
CYP17
for hypoxia adaptability in Tibetan sheep and
DNAJB5
for heat tolerance in Duolang sheep. Our findings provide insights into the genetic mechanisms underlying important phenotypic changes that have occurred during sheep domestication and subsequent selection.
It is well established that cannabis use promotes appetite. However, how cannabis interacts with the brain’s appetite center, the hypothalamus, to stimulate feeding behavior is unknown. A growing body of evidence indicates that the hypothalamic transcriptome programs energy balance. Here, we tested the hypothesis that cannabis targets alternative polyadenylation (APA) sites within hypothalamic transcripts to regulate transcriptomic function. To do this, we used a novel cannabis vapor exposure model to characterize feeding in adult male Long Evans rats and aligned this behavioral response with APA events using a Whole Transcriptome Termini Sequencing (WTTS-Seq) approach as well as functional RNA abundance measurements with real-time quantitative polymerase chain reactions. We found that vapor cannabis exposure promoted food intake in free-feeding and behaviorally sated rats, validating the appetite stimulating properties of cannabis. Our WTTS-Seq analysis mapped 59 unique cannabis-induced hypothalamic APAs that occurred primarily within exons on transcripts that regulate synaptic function, excitatory synaptic transmission, and dopamine signaling. Importantly, APA insertions regulated RNA abundance of Slc6a3, the dopamine transporter, suggesting a novel genetic link for cannabis regulation of brain monoamine function. Collectively, these novel data indicate that a single cannabis exposure rapidly targets a key RNA processing mechanism linked to brain transcriptome function.
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