DFT study on isothiourea-catalyzed C-C bond activation of cyclobutenone: the role of the catalyst and the origin of stereoselectivity.

The organocatalytic C-C bond activation strategy stands out as a new reaction mode for the release of ring strain and expands the scope of organocatalysts. Thus, disclosing the role of the organocatalyst in the C-C bond cleavage process would be of interest. Here, an isothiourea-catalyzed C-C bond activation/cycloaddition reaction of cyclobutenone is selected as a computational model to uncover the role of the catalyst. Based on the calculations, the electrocyclic cleavage of cyclobutenone is calculated to be energetically more favorable than the isothiourea-catalyzed C-C bond cleavage, which is different from the NHC-catalyzed C-C bond activation of cyclobutenone. The computational results show that the isothiourea promotes the reaction by increasing the nucleophilicity of vinyl ketene and thus lowers the energy barrier of the cycloaddition process. Moreover, NCI and AIM analyses are performed to disclose the origin of stereoselectivity.

Research on Improving Radiotherapy Accuracy Based on Image-Guided Radiotherapy.

With the changes of people's diet and lifestyle, the number of patients with abdominal malignant tumors is increasing year by year. In order to analyze the effectiveness of cone-beam CT (CBCT) enhancement technology in improving the accuracy of radiotherapy for clinical malignant tumors, 92 patients with abdominal malignant tumor are divided into the control group and the CBCT radiotherapy group. The experimental results show that precise radiotherapy technology can promote the recovery of the immune function of patients with abdominal malignant tumors, improve the effect of treatment, and decrease the incidence of complications.

Rational surface modification of gadolinium borate nanoparticles enhancing colloidal stability in physiological media for potential neutron capture therapy and magnetic resonance imaging.

Colloidal stability of nanomaterials in physiological media is an indispensable property for their biomedical applications. However, gadolinium borate (GdBO3) nanoparticles that hold promise as a theranostic agent for neutron capture therapy (NCT) and magnetic resonance imaging (MRI) of cancer tend to precipitate in phosphate buffered saline (PBS) owing to formation of insoluble gadolinium phosphate. To address this issue, in this work 10B-enriched GdBO3 nanoparticles were prepared and coated with mesoporous silica (mSiO2) of ~ 40 nm in thickness and subsequently grafted with hydrophilic polyglycerol (PG). The resulting GdBO3 @mSiO2-PG nanoparticles showed excellent colloidal stability in PBS due to the protection of the mSiO2 coating as well as superior dispersibility because of the high hydrophilicity of the PG layer. In vitro experiments revealed that GdBO3 @mSiO2-PG possessed low cytotoxicity and could be taken up by cancer cells in a concentration-dependent manner. In vivo studies indicated that GdBO3 @mSiO2-PG can circulate in mouse body for a considerably long time without obvious acute toxicity. In addition, GdBO3 @mSiO2-PG also showed promise as a T1-weighted MRI contrast agent with a proton longitudinal relaxivity of 0.67 mM-1 s-1. Our results indicate that GdBO3 @mSiO2-PG with enhanced colloidal stability in physiological media could serve as a promising multifunctional agent for cancer theranostics.

SPECT imaging and highly efficient therapy of rheumatoid arthritis based on hyperbranched semiconducting polymer nanoparticles.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Although significant progress has been made in clinical treatment, joint inflammation may continue or worsen, and may even progress to the end-stage that requires joint replacement. Traditional therapy using methotrexate (MTX) would cause serious off-target systemic toxicities. Therefore, it is crucial to effectively and specifically deliver MTX to targeted inflamed joints to decrease its adverse systemic toxicities and improve its therapeutic index. Herein, we develop multifunctional nanocarriers for diagnostic radioisotope (99mTc) labeling and therapeutic targeted drug (MTX) delivery by using PEGylated hyperbranched semiconducting polymer nanoparticles (HSP-PEG-NPs) as carriers. Upon intravenous administration, the nanoparticles can extravasate through the turbulent blood-joint barrier and access the inflamed joints. In vivo SPECT/CT imaging shows high accumulation in the inflamed joints of mice with RA after intravenous injection of HSP-PEG-NPs with 99mTc labeling (99mTc-HSP-PEG). In vivo therapeutic evaluations suggest that MTX@HSP-PEG-NPs significantly alleviate RA with a high therapeutic index and relatively low adverse systemic toxicities in comparison with free MTX at the same dose. Our study shows that HSP-PEG-NPs could serve as multifunctional vehicles to deliver radioisotopes for in vivo imaging, and MTX for RA treatment, highlighting the innovative development of the nanoparticle-based RA treatment strategy for clinical applications.

Detection of white matter lesions in the acute stage of diffuse axonal injury predicts long-term cognitive impairments: a clinical diffusion tensor imaging study.

BACKGROUND: White matter disruption is known to contribute to neurocognitive deficits after diffuse axonal injury (DAI). This study evaluated the relationship between white matter integrity using diffusion tensor imaging in the early stage and cognitions in the chronic stage. METHODS: Diffusion tensor imaging was performed in 15 patients with DAI within 7 days of injury and in 15 patients in the control group. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated within regions of interest, including the posterior limb of the internal capsule, uncinate fasciculus (UF), anterior corona radiate (ACR), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), genu of the corpus callosum, body of the corpus callosum, and splenium of the corpus callosum and cingulum bundle (CB). The patients with DAI and the patients in the control group also underwent neuropsychological testing during the chronic stage after DAI. RESULTS: The region-of-interest analysis showed significantly reduced FA and AD values in all nine regions within 7 days of injury as well as increased MD values in the corpus callosum among patients in the DAI group. The patients demonstrated significantly poorer performance on the working memory tests and attention test. In patients, working memory function was positively correlated with the AD value in the UF and with the FA value in the CB, UF, SLF, and ILF. Working memory function was inversely correlated with the RD value in the CB, SLF, and ILF and with the MD value in the SLF and ILF. In addition, the attention function demonstrated a positive correlation with the RD value in the ACR, SLF, and ILF and with the MD value in the ACR, SLF, and ILF. In addition, attention was inversely correlated with the FA values for the posterior limb of the internal capsule, ACR, SLF, and ILF. CONCLUSION: The results indicated that the presence of white matter changes during the early stage of DAI may be helpful for predicting cognitive dysfunction over the long term. LEVEL OF EVIDENCE: Prognostic study, level III.