Synergistic therapy that combines chemo-, gene-, or photothermal means shows great potential for enhancing the therapeutic effects on cancers. Tumor-targeted nanoparticles based on a doxorubicin (DOX)-gated mesoporous silica nanocore (MSN) encapsulated with permeability glycoprotein (P-gp) small interfering RNA (siRNA) and a polydopamine (PDA) outer layer for DOX loading and folic acid decoration are designed. The multifunctional nanoplatform tactfully integrates chemo-(DOX), gene-(P-gp siRNA), and photothermal (PDA layer) substances in one system. In vitro results reveal that DOX release behaviors are both pH-and thermal-responsive and the release of co-delivered P-gp siRNA is also pH-dependent due to the pH-cleavable DOX gatekeeper on MSN. In addition, due to the near-infrared light-responsive PDA outer layer and folic acid conjugation, the nanoparticles exhibit outstanding photothermal activity and selective cell targeting ability. Subsequently, in vitro and in vivo antitumor experiments both demonstrate the enhanced antitumor efficacy of the multifunctional nanoparticles, indicating the significance of synergistic therapy combining chemo-, gene-, and photothermal treatments in one system. Cancer Therapy

No abstract

This study was designed to conclude the ultrasonic characteristics of uterosacral ligament (USL) lesions involved by endometriosis and evaluated the value of transvaginal sonography (TVS) in diagnosing USL involvement in deep infiltrating endometriosis (DIE). A total of one hundred and eighteen patients with DIE were included in the study and underwent surgery. All these patients were evaluated by transvaginal ultrasound examination by one trained examiner. The gold standard for diagnosis was surgery and histopathology. 85 patients with USL endometriosis were confirmed by surgical pathology. 84 patients were diagnosed USL endometriosis by TVS and 81 of which were confirmed by the gold standard. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of TVS for diagnosing USL endometriosis were 95.3, 90.9, 96.4, 88.2, and 94.1%, respectively. According to the ultrasound characteristics of USL endometriosis, we summarized four types: Type I. thickened and stiff lesions, Type II. local nodules, Type III. irregular striped lesions, and Type IV. mixed lesions. The conclusion of the study was that TVS was a convenient, accurate and first-line diagnostic technique for USL endometriosis and the USL lesions could be summarized into four types according to the ultrasound morphological changes.

Highly diversified astigmatic mites comprise many medically important human household pests such as house dust mites causing approximately 1–2% of all allergic diseases globally; however, their evolutionary origin and diverse lifestyles including reversible parasitism have not been illustrated at the genomic level, which hampers allergy prevention and our exploration of these household pests. Using six high-quality assembled and annotated genomes, this study not only refuted the monophyly of mites and ticks, but also thoroughly explored the divergence of Acariformes and the diversification of astigmatic mites. In monophyletic Acariformes, Prostigmata known as notorious plant pests first evolved, and then rapidly evolving Astigmata diverged from soil oribatid mites. Within astigmatic mites, a wide range of gene families rapidly expanded via tandem gene duplications, including ionotropic glutamate receptors, triacylglycerol lipases, serine proteases and UDP glucuronosyltransferases (UGTs). Gene diversification after tandem duplications provides many genetic resources for adaptation to sensing environmental signals, digestion, and detoxification in rapidly changing household environments. Many gene decay events only occurred in the skin-burrowing parasitic mite Sarcoptes scabiei. Throughout the evolution of Acariformes, massive horizontal gene transfer events occurred in gene families such as UGTs and several important fungal cell wall lytic enzymes, which enable detoxification and digestive functions and provide perfect drug targets for pest control. This comparative study sheds light on the divergent evolution and quick adaptation to human household environments of astigmatic mites and provides insights into the genetic adaptations and even control of human household pests.