Controlled CRISPR-Cas9 Ribonucleoprotein Delivery for Sensitized Photothermal Therapy.

Manipulation of CRISPR delivery for stimuli-responsive gene editing is crucial for cancer therapeutics through maximizing efficacy and minimizing side-effects. However, realizing controlled gene editing for synergistic combination therapy remains a key challenge. Here, a near-infrared (NIR) light-triggered thermo-responsive copper sulfide (CuS) multifunctional nanotherapeutic platform is constructed to achieve controlled release of CRISPR-Cas9 ribonucleoprotein (RNP) and doxorubicin for tumor synergistic combination therapy involving in gene therapy, mild-photothermal therapy (PTT), and chemotherapy. The semiconductor CuS serves as a "photothermal converter" and can stably convert NIR light (808 nm) into local thermal effect to provide photothermal stimulation. The double-strand formed between CuS nanoparticle-linked DNA fragments and single-guide RNA is employed as a controlled element in response to photothermal stimulation for controlled gene editing and drug release. Hsp90α, one subunit of heat shock protein 90 (Hsp90), is targeted by Cas9 RNP to reduce tumor heat tolerance for enhanced mild-PTT effects (≈43 °C). Significant synergistic therapy efficacy can be observed by twice NIR light irradiation both in vitro and in vivo, compared to PTT alone. Overall, this exogenously controlled method provides a versatile strategy for controlled gene editing and drug release with potentially synergistic combination therapy.

Spatially differentiated effects of socioeconomic factors on China's NOx generation from energy consumption: implications for mitigation policy.

Nitrogen oxides (NOx) has become the priority of China's air pollution control, but the regional socio-economic factors responsible for NOx generation are embedded with spatial disparities, which leads to different effects of air quality policy at the local level. This study applied a geographically weighted regression (GWR) model to investigate the drivers of NOx generation from energy consumption (NGEC) in China's 30 provinces, to explore nonstationary spatial effects of NGEC. The results showed that population size has always been the dominant factor in spatial NGEC across all regions of China, although there is a minor north-south difference. However, the effect of per capita GDP and energy intensity leads to a significant north-south difference when they are influencing NGEC, which shows a minor west-east difference from thermal power generation (TE). We also found that in Northern and Northeast China, the transition towards cleaner energy structure based on natural gas has started correlating significantly with NOx generation through a weakly negative effect in 2015. Our findings show alternative strategies on NOx reduction, which include the spatially differentiated effect of regional socioeconomic factors on energy consumption.

Comparative analysis of the performance of hepatobiliary agents in depicting MRI features of microvascular infiltration in hepatocellular carcinoma.

OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.

Exploration of Clove Bud (Syzygium aromaticum) Essential Oil as a Novel Attractant against Bactrocera dorsalis (Hendel) and Its Safety Evaluation.

The oriental fruit fly Bactrocera dorsalis (Hendel) is a destructive polyphagous species that targets many economically important fruits and vegetables. The primary control of B. dorsalis relies mainly on the use of synthetic chemicals, and excessive use of these chemicals has adverse effects on both the environment and human health. Environmentally friendly management of pests involving plant essential oils is useful for controlling the populations of pests responsible for decreasing the yields and quality of crops. In the present study, we demonstrate that clove bud essential oil (CBEO) is strongly attractive to sexually mature males. Mature males responded to the CBEO differently throughout the day; the strongest response was elicited during the day and decreased at dusk. Virgin and mated mature males did not respond differently to CBEO. No obvious response behaviour to the CBEO was observed in two species of beneficial natural predator ladybirds. In addition, a cytotoxicity assessment demonstrated that CBEO is nontoxic to normal human and mouse cells. Based on our laboratory experiments, CBEO may serve as a promising, sustainable, and environmentally friendly attractant for B. dorsalis males; however, field experiments are needed to confirm this hypothesis.