Safe and efficient 2D molybdenum disulfide platform for cooperative imaging-guided photothermal-selective chemotherapy: A preclinical study

Introduction: The striking imbalance between the ever-increasing amount of nanomedicines and low clinical translation of products has become the focus of intense debate. For clinical translation, the critical issue is to select the appropriate agents and combination regimen for targeted diseases, not to prepare increasingly complex nanoplatforms. Objectives: A safe and efficient platform, α-tocopheryl succinate (α-TOS) married 2D molybdenum disulfide, was devised by a facile method and applied for cooperative imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Methods: A novel platform of PEGylated α-TOS and folic acid (FA) conjugated 2D MoS2 nanoflakes was fabricated for the cooperative multimode computed tomography (CT)/photoacoustic (PA)/thermal imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Results: The photothermal efficiency (65.3%) of the platform under safe near-infrared irradiation is much higher than that of other photothermal materials reported elsewhere. Moreover, the covalently linked α-TOS renders platform with selective chemotherapy for cancer cells. Remarkably, with these excellent properties, the platform can be used to completely eliminate the solid tumor by safe photothermal therapy, and then kill the residual cancer cells by selective chemotherapy to prevent tumor recurrence. More significantly, barely side effects occur in the whole treatment process. The excellent efficacy and safety benefits in vivo lead to the prominent survival rate of 100% over 91 days. Conclusion: The safe and efficient platform might be a candidate of clinical nanomedicines for multimode theranostics. This study demonstrates an innovative thought in precise nanomedicine regarding the design of next generation of cancer theranostic protocol for potential clinical practice

Altered Brain Activities Associated with Craving and Cue Reactivity in People with Internet Gaming Disorder: Evidence from the Comparison with Recreational Internet Game Users

Although the neural substrates of cue reactivity in Internet gaming disorder (IGD) have been examined in previous studies, most of these studies focused on the comparison between IGD subjects and healthy controls, which cannot exclude a potential effect of cue-familiarity. To overcome this limitation, the current study focuses on the comparison between IGD subjects and recreational Internet game users (RGU) who play online games recreationally but do not develop dependence. Data from 40 RGU and 30 IGD subjects were collected while they were performing an event-related cue reactivity task in the fMRI scanner. The results showed that the IGD subjects were associated with enhanced activation in the left orbitofrontal cortex (OFC) and decreased activation in the right anterior cingulate cortex (ACC), right precuneus, left precentral gyrus and right postcentral gyrus in comparison with the RGU subjects. OFC is involved in reward evaluation and ACC is implicated in executive control function based on previous researches. Moreover, the activation of OFC were correlated with the desire for game-playing. Thus, the higher activation in OFC might suggests high desire for game playing, and the lower activation in ACC might indicates impaired ability in inhibiting the urge to gaming-related stimuli in IGD subjects. Additionally, decreased activation in the precuneus, the precentral and postcentral gyrus may suggest the deficit in disentangling from game-playing stimuli. These findings explain why IGD subjects develop dependence on game-playing while RGU subjects can play online games recreationally and prevent the transition from voluntary game-playing to eventually IGD

The impact of sexual intercourse during pregnancy on obstetric and neonatal outcomes: a cohort study in China

The reports about the effects of sexual attitudes and activities on obstetric outcomes were inconsistent or even contradictory. This study aims to investigate the patterns of sexual intercourse during pregnancy and its impact on obstetric and neonatal outcomes. All of the participants delivered their babies between September 2016 and June 2017 at Peking Union Medical College Hospital (PUMCH). An online questionnaire was sent to postpartum women with singleton deliveries at least 6 months after their deliveries. The perinatal outcome data were collected by reviewing the maternal and neonatal medical records. The obstetric and neonatal outcomes were compared between the women without and with sexual intercourse. Five hundred fifty questionnaires were sent out, and 406 (73.8%) women responded. A total of 211 (52%) women had sexual intercourse during pregnancy. There were 113, 67, 22, and 9 women reporting frequencies of sexual intercourse of less than once per month, 1–2 times/month, 3–4 times/month, and >4 times/month, respectively, and 49, 199, and 59 women reported sexual intercourse during their first, second, and third trimesters. The most common complaint was a lack of sexual interest. The experiences, frequency, and timing of sexual intercourse had no significant impact on any obstetric or neonatal outcome compared with those of the women without sexual intercourse.Impact statement What is already known on this subject? The reports about the effects of sexual attitudes and activities on obstetric outcomes were inconsistent. What do the results of this study add? In our study, the experiences, frequency, and the timing of sexual intercourse had no significant impact on any obstetric or neonatal outcome compared with those of women without sexual intercourse. What are the implications of these findings for clinical practice and/or further research? Sexual intercourse is generally safe in healthy pregnant women

Photocatalytic Reduction Activity of 001 TiO2 Codoped with F and Fe under Visible Light for Bromate Removal

The presence of bromate in water is a well-known problem because of its toxic effects on human health, particularly its carcinogenic potential. Photocatalytic reduction is an attractive process for bromate removal. F- and Fe-codoped TiO2 (F-Fe-TiO2) with a {001} facet was successfully prepared, and its bromate-removal activity under visible light was examined. The microstructure, morphology, and chemical state of the doping elements and the optical property of the photocatalysts were examined using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), photoluminescence spectroscopy (PLS), and UV-Vis diffuse reflectance spectra (DRS). The results indicate that the optical properties of F-Fe-TiO2 with the {001} facet and cuboid morphology were obviously improved and its photocatalytic activity was significantly enhanced. The bromate solution of 100 μg/L was thoroughly removed with 0.5 g/L dosage of 1.0% F- and 0.08% Fe-codoped TiO2 composite within 1 hour under visible light

Management of non-pharmacologic therapy for chronic refractory cough: Mechanism, composition, applicable population, and assessment

Chronic cough is common in the clinic and can seriously affect the quality of life of patients. Following the existing guidelines for treatment, refractory chronic cough is defined as a clinical condition in which the cause of the cough remains unclear after comprehensive examination and treatment, or the cause is clear but symptomatic treatment is ineffective.It has been found that non-pharmacologic therapy can effectively improve the quality of life and reduce the frequency of coughing for some patients with refractory chronic cough. Compared with pharmacological therapy, non-pharmacologic therapy has no obvious adverse effects; therefore, non-pharmacologic therapy has good application prospects in the diagnosis and treatment of refractory chronic cough. This paper summarizes the composition, indication, action and mechanism of non-pharmacologic therapy in the diagnosis and treatment of refractory chronic cough and prospects for research on non-pharmacologic therapy

The complete chloroplast genome of Zelkova serrata and its phylogenetic position within Ulmaceae

The complete chloroplast genome sequence of the Tertiary relict tree Zelkova serrata was reported in this study. The chloroplast genome is 158,875 bp in length with a typical angiosperm quantitative structure consisting of a large single copy (87,412 bp) and a small single copy (18,683 bp) separated by a pair of inverted repeat (26,390 bp). Genome annotation revealed a total of 129 genes comprising 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenomic analysis based on the whole plastomes indicated that Z. serrata and Z. schneideriana formed a well-supported monophyletic clade sister to genus Ulmus in Ulmaceae

Altered Brain Activities Associated with Craving and Cue Reactivity in People with Internet Gaming Disorder : Evidence from the Comparison with Recreational Internet Game Users

Although the neural substrates of cue reactivity in Internet gaming disorder (IGD) have been examined in previous studies, most of these studies focused on the comparison between IGD subjects and healthy controls, which cannot exclude a potential effect of cue-familiarity. To overcome this limitation, the current study focuses on the comparison between IGD subjects and recreational Internet game users (RGU) who play online games recreationally but do not develop dependence. Data from 40 RGU and 30 IGD subjects were collected while they were performing an event-related cue reactivity task in the fMRI scanner. The results showed that the IGD subjects were associated with enhanced activation in the left orbitofrontal cortex (OFC) and decreased activation in the right anterior cingulate cortex (ACC), right precuneus, left precentral gyrus and right postcentral gyrus in comparison with the RGU subjects. OFC is involved in reward evaluation and ACC is implicated in executive control function based on previous researches. Moreover, the activation of OFC were correlated with the desire for game-playing. Thus, the higher activation in OFC might suggests high desire for game playing, and the lower activation in ACC might indicates impaired ability in inhibiting the urge to gaming-related stimuli in IGD subjects. Additionally, decreased activation in the precuneus, the precentral and postcentral gyrus may suggest the deficit in disentangling from game-playing stimuli. These findings explain why IGD subjects develop dependence on game-playing while RGU subjects can play online games recreationally and prevent the transition from voluntary game-playing to eventually IGD.publishe

Enhanced Delivery of Therapeutic siRNA into Glioblastoma Cells Using Dendrimer-Entrapped Gold Nanoparticles Conjugated with β-Cyclodextrin

We describe a safe and highly effective non-viral vector system based on β-cyclodextrin (β-CD)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for improved delivery small interfering RNA (siRNA) to glioblastoma cells. In our approach, we utilized amine-terminated generation 5 poly(amidoamine) dendrimers partially grafted with β-CD as a nanoreactor to entrap Au NPs. The acquired β-CD-modified Au DENPs (Au DENPs-β-CD) were complexed with two different types of therapeutic siRNA (B-cell lymphoma/leukemia-2 (Bcl-2) siRNA and vascular endothelial growth factor (VEGF) siRNA). The siRNA compression ability of the Au DENPs-β-CD was evaluated by various methods. The cytocompatibility of the vector/siRNA polyplexes was assessed by viability assay of cells. The siRNA transfection capability of the formed Au DENPs-β-CD vector was evaluated by flow cytometric assay of the cellular uptake of the polyplexes and Western blot assays of the Bcl-2 and VEGF protein expression. Our data reveals that the formed Au DENPs-β-CD carrier enables efficiently delivery of siRNA to glioma cells, has good cytocompatibility once complexed with the siRNA, and enables enhanced gene silencing to inhibit the expression of Bcl-2 and VEGF proteins. The developed Au DENPs-β-CD vector may be used for efficient siRNA delivery to different biosystems for therapeutic purposes

Enhanced delivery of therapeutic siRNA into glioblastoma cells using dendrimer-entrapped gold nanoparticles conjugated with β-cyclodextrin

International audienceWe describe a safe and highly effective non-viral vector system based on β-cyclodextrin (β-CD)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for improved delivery small interfering RNA (siRNA) to glioblastoma cells. In our approach, we utilized amine-terminated generation 5 poly(amidoamine) dendrimers partially grafted with β-CD as a nanoreactor to entrap Au NPs. The acquired β-CD-modified Au DENPs (Au DENPs-β-CD) were complexed with two different types of therapeutic siRNA (B-cell lymphoma/leukemia-2 (Bcl-2) siRNA and vascular endothelial growth factor (VEGF) siRNA). The siRNA compression ability of the Au DENPs-β-CD was evaluated by various methods. The cytocompatibility of the vector/siRNA polyplexes was assessed by viability assay of cells. The siRNA transfection capability of the formed Au DENPs-β-CD vector was evaluated by flow cytometric assay of the cellular uptake of the polyplexes and Western blot assays of the Bcl-2 and VEGF protein expression. Our data reveals that the formed Au DENPs-β-CD carrier enables efficiently delivery of siRNA to glioma cells, has good cytocompatibility once complexed with the siRNA, and enables enhanced gene silencing to inhibit the expression of Bcl-2 and VEGF proteins. The developed Au DENPs-β-CD vector may be used for efficient siRNA delivery to different biosystems for therapeutic purposes

Mn(OAc)₃‑Promoted Oxidative C_sp³–P Bond Formation through C_sp²–C_sp² and P–H Bond Cleavage: Access to β‑Ketophosphonates

The Mn­(OAc)₃-promoted oxidative phosphonylation of <i>N</i>,<i>N</i>-dimethylenaminones with H-phosphonates, involving a chemo- and regioselective C_sp²–C_sp² bond cleavage and C_sp³–P bond formation in one step, provided successfully functionalized β-ketophosphonates under mild reaction conditions. Oxidative C_sp³–H/P–H cross-coupling reactions via C_sp³–C­(CO) bond cleavage and mechanistic studies are conducted preliminarily, and a possible mechanism is proposed. This novel method proceeds in good to excellent yields, shows operational simplicity, broad substrate scope, and large-scale preparation