The clustered, regularly interspaced short palindromic repeats-associated protein 9 endonuclease (CRISPR-Cas9) and the nuclease-deactivated Cas9 (dCas9) systems have revolutionized our ability to precisely engineer and regulate genomes. Inducible CRISPR-dCas9-based transcriptional systems have been rapidly developed to conditionally control genetic manipulation. Current strategies mainly focus on conditional control of gRNA function and dCas9 protein using exogenous and endogenous triggers, including external light, small molecules, synthetic and intracellular oligonucleotides. These strategies have established novel platforms for the spatiotemporal regulation of genome activation and repression, epigenome editing, and so on. Herein, we summarize the recent progress in conditionally controlling CRISPR-dCas9 transcriptional systems through gRNA modulation and dCas9 protein engineering.The site-selective functionalization of C-H bonds within a complex molecule remains a challenging task of capital synthetic importance. Herein, an unprecedented Pd-catalyzed C(sp2 )-H alkoxycarbonylation of phenylalanine derivatives and other amines featuring picolinamide as the directing group (DG) is reported. This oxidative coupling is distinguished by its scalability, operational simplicity, and avoids the use of toxic carbon monoxide as the C1 source. Remarkably, the easy cleavage of the DG enables the efficient assembly of isoindolinone compounds. Density Functional Theory calculations support a PdII /PdIV catalytic cycle.When powder is applied to the genital area, it has the potential to reach internal reproductive organs and promote carcinogenesis by irritating and inflaming exposed tissues. Although many studies have considered the association between genital powder use and ovarian cancer risk, the relationship between genital powder use and uterine cancer is less well-studied. We pooled data from four large, prospective cohorts (the Nurses’ Health Study, the Nurses’ Health Study II, the Sister Study and the Women’s Health Initiative – Observational Study). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for prespecified confounders. In total, 209 185 women were included, with 37% reporting ever genital powder use. Over a mean 14.5 years of follow-up, 3272 invasive uterine cancers were diagnosed. There was no overall association between ever genital powder use and uterine cancer (HR = 1.01, 95% CI 0.94-1.09), with little difference observed for frequent (≥1 times/week) vs never use (HR = 1.05, 95% CI 0.95-1.16; P-for-trend = .46). Long-term use (>20 years; HR = 1.12, 95% CI 0.96-1.31; P-for-trend = 0.14) was associated with a small, but not statistically significant, increase in risk, compared to never use. There were not clear differences by uterine cancer histologic subtypes or across strata of relevant covariates, including race/ethnicity, follow-up time, menopausal status and body mass index. The results of this large, pooled analysis do not support a relationship between the use of genital powder and uterine cancer, although the positive associations observed for long-term use may merit further consideration.While wing form is known to differ between males and females of the genus Culicoides, detailed studies of sexual dimorphism are lacking. In this study, we analyze sex-specific differences in the wing form of 5 species of the subgenus Avaritia, using geometric morphometrics and comparative phylogenetic methods. Our results confirm the existence of marked sexual dimorphism in the wing form of the studied species and reveal for the first time that while there is a shared general pattern of sexual shape dimorphism within the subgenus, sexual size dimorphism, and particular features of sexual shape dimorphism differ among species. Sexual shape dimorphism was found to be poorly associated to size and the evolutionary history of the species. The tight association of sexual shape dimorphism with aspect ratio suggests that the shape of the wing is optimized for the type of flight of each sex, that is, dispersal flight in females versus aerobatic flight in males. Moreover, the fact that interspecific shape differences are greater and more strongly associated to aspect ratio in males than in females might be indicating that in males the selective pressures affecting flight performance characteristics are more heterogeneous and/or stronger than in females among the studied species.

The purpose of this study is to compare the safety and outcomes of percutaneous radiologic gastrostomy (PRG) in obese vs nonobese patients.

This is an institutional review board-approved retrospective study of 109 patients (malefemale, 6841; mean age, 64.7 years; range, 21-94 years) who underwent PRG with or without gastropexy at a single academic medical center between 2015 and 2018. Body mass index (BMI) of ≥30 kg/m

was defined as obese. Patient demographics, indications, technical success, intraoperative variables, and major/minor complications were analyzed. find more Major and minor complications occurring within 30 days of the procedure were recorded and categorized based on the Society of Interventional Radiology Quality Improvement guidelines.

Of 109 patients included in the study, 22.9% (n = 25) of patients were obese (average BMI, 34.6 kg/m

; range, 30-50). Overall technical success in the obese and nonobese groups was 100% each. In the obese vs nonobese group, major and minor complications were not significantly different. There were also no significant differences in procedure time, fluoroscopy time, or contrast volume. However, mean peak skin dose was significantly increased in the obese group vs nonobese group (190.3 ± 224.2 vs 59.1 ± 71.1 mGy; P < .0001).

PRG is a safe procedure in obese patients with similar technical success, major and minor complication rates, procedure time, fluoroscopy time, and contrast volume. However, PRG is associated with increased radiation dose with obese patients; therefore, optimal methods of radiation protection should be utilized.

PRG is a safe procedure in obese patients with similar technical success, major and minor complication rates, procedure time, fluoroscopy time, and contrast volume. However, PRG is associated with increased radiation dose with obese patients; therefore, optimal methods of radiation protection should be utilized.