Rational design of cuprofullerene bipyridine nanozyme with high peroxidase-like activity for colorimetric sensing of bleomycin.

The high catalytic activity of Cu-based nanozymes mainly depends on the efficient Fenton-like reaction of Cu+/ H2O2, but Cu+ cannot exist stably. Trying to find a material that can stably support Cu+ while promoting the electron cycle of Cu2+/Cu+ still faces serious challenges. C60 is expected to be an ideal candidate to solve this problem due to its unique structure and rich physicochemical properties. Here, we designed and synthesized a C60-doped Cu+-based nanozyme (termed as C60-Cu-Bpy) by loading high catalytic active site Cu+ onto C60 and coordinating with 2,2'-bipyridine (Bpy). The single crystal diffraction analysis and a series of auxiliary characterization technologies were used to demonstrate the successful preparation of C60-Cu-Bpy. Significantly, the C60-Cu-Bpy exhibited superior peroxidase-like activity during the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). Then, the catalytic mechanism of C60-Cu-Bpy as peroxidase was elucidated in detail, mainly benefiting from the dual function of C60. On the one hand, C60 acted as a carrier to directly support Cu+, which has the ability to efficiently decompose H2O2 to produce reactive oxygen species. The other was that C60 acted as an electron buffer, contributing to promoting the Cu2+/Cu+ cycle to facilitate the reaction. Furthermore, a colorimetric sensor for the quantitative analysis of bleomycin was established based on the principle of bleomycin specific inhibition of C60-Cu-Bpy peroxidase-like activity, with satisfactory results in practical samples. This study provides a new strategy for the direct synthesis of Cu+-based nanozymes with high catalytic performance.

Curcuminoids Modulated the IL-6/JAK/STAT3 Signaling Pathway in LoVo and HT-29 Colorectal Cancer Cells.

BACKGROUND: Curcuminoids, including curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin, are natural polyphenolic compounds that exhibit various biological properties, such as antioxidant, anti-inflammatory, and anticancer activities. Dysregulation of the interleukin (IL)-6-mediated Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway is closely associated with the development of colorectal cancer (CRC). METHODS: Here, we have evaluated the modulation of the IL-6/JAK/STAT3 pathway of curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin in LoVo and HT-29 colorectal cancer cells with a single molecular array (Simoa), western blot analysis, real-time polymerase chain reaction (PCR), and pathway analysis system. RESULTS: The study showed that curcuminoids suppressed the amount of IL-6 in LoVo and HT-29 colorectal cancer cells. Meanwhile, curcuminoids inhibited the expression of inflammation regulator-related microRNA (miRNA). We also found that the expression of total STAT3 was downregulated by curcuminoids. Moreover, the pathway analysis system showed that curcuminoids inactivated the JAK/STAT3 signaling pathway. Taken together, we demonstrated that the anti-cancer activities of curcuminoids against colorectal cancer are due to the modulation of the IL-6/JAK/STAT3 cascade. CONCLUSION: Curcuminoids could be a promising anti-cancer agent for the treatment of human colorectal cancer.

Shenlian extract protected ox-LDL-loaded macrophages against ER stress by promoting LAL-LXRα mediated cholesterol flux.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenlian (SL) extract is consisted of extracts from Salvia miltiorrhiza Bunge and Andrographis paniculata (Burm.f.) Nees, two herbs commonly used in Chinese clinical formula to treat atherosclerosis by removing blood stasis and clearing away heat. Pharmacologically, the anti-atherosclerotic effects of these two herbs are related to unresolved inflammation and the macrophage anergy or apoptosis in lesions led by the lipid flux blockage and ER stress. However, the deeper understanding of SL extract in protecting macrophage in plaques remains unknown. AIM OF THE STUDY: This study aimed to investigate the underlying mechanism of SL extract in protecting ER-stressed macrophages from apoptosis in atherosclerosis. METHODS: The ApoE-/- atherosclerotic mice model and ox-LDL loaded macrophages model were established to assess the effect of SL extract on ER stress in vivo and in vitro. Key markers related to ER stress in plaque were determined by immunohistochemical staining. Proteins involved in apoptosis and ER stress in macrophages loaded by ox-LDL were assessed by Western blot. ER morphology was observed by electron microscope. Lipid flux was temporally and quantitatively depicted by Oil red staining. The LAL and LXRα were blocked by lalistat and Gsk 2033 respectively to investigate whether SL extract protected the function of macrophages by the activation of LAL-LXRα axis. RESULTS: Our study reported that, in ApoE-/- atherosclerotic mice, SL extract effectively relieved ER stress of carotid artery plaque. In lipid-overloaded macrophage models, SL extract significantly alleviated ER stress by promoting cholesterol degradation and efflux, which finally prevented apoptosis of foam cells induced by ox-LDL. Blockage of ER stress by 4-Phenylbutyric acid (4-PBA), an inhibitor of Endoplasmic Reticulum (ER) stress, largely attenuated the protective effects of SL extract on macrophage. By utilizing the selective antagonists against both LAL and LXRα, this study further revealed that the beneficial effects of SL extract in macrophages was dependent on the proper functionalization of LAL-LXRα axis. CONCLUSIONS: By highlighting the therapeutic significance of macrophage protection in resolving atherosclerosis inflammation, our study pharmacologically provided convincing mechanistic evidence of SL extract in the activation LAL-LXRα axis and revealed its promising potential in the promotion of cholesterol turnover and prevention of ER stress induced apoptosis in lipid-loaded macrophages.

[Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling].

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Ginsenoside Rg1 promotes remyelination and functional recovery in demyelinating disease by enhancing oligodendrocyte precursor cells-mediated myelin repair.

BACKGROUND: Inefficient differentiation of oligodendrocyte precursor cells (OPCs) is one of the significant pathological obstacles of myelin repair and provides an essential therapeutic target against behavioral dysfunction in various neurodegenerative diseases, especially in secondary progressive multiple sclerosis (SPMS). Ginsenoside Rg1 (Rg1) has traditionally been recognized as a protector of neuronal damages, preventing its degeneration. PURPOSE: We investigated the effects of Rg1 on myelin regeneration-mediated by OPCs and its therapeutic significance in SPMS. METHODS: A cuprizone (CPZ) model was established and then administered with Rg1 specific for evaluations of functional recovery and remyelination. In vitro, the primary mouse OPCs were isolated and cultured for examining their ability of myelin repair. Furthermore, a chronic experimental autoimmune encephalomyelitis (EAE) model was utilized to assess the therapeutic value on SPMS. RESULTS: We found that Rg1 promoted functional recovery of the demyelinated mice, including spatial memory, motor function, and anxiety-like behavior. Histologically, Rg1 enhanced myelin-genesis as proven by myelin staining and microstructures of myelin observed by transmission electron microscope. Furthermore, Rg1 significantly increased Olig2+ oligodendrocyte lineage cells in callosum, implying that the pro-remyelination effect of Rg1 was closely correlated to the enhanced differentiation of OPCs. We further demonstrated that Rg1 increased the survival and proliferation of OPCs as well as induced maturation in oligodendrocytes (OLs). Molecular analysis showed that Rg1 transduced the pro-differentiation signaling programmed by the GSK3ß/ß-Catenin pathway. Notably, relying on its pro-remyelination effects, Rg1 ameliorated severity and histopathology of EAE disease. CONCLUSION: By paving the way for OPCs differentiation, Rg1 could maintain the integrity of myelin and is a promising candidate for functional recovery in demyelinating diseases.

Inclusive education of elementary students with autism spectrum disorders in Shanghai, China: From the teachers' perspective.

Given an increasing number of children with ASD, the need for inclusive education has rapidly increased in China. Since 2011, children with ASD have been eligible for inclusive education. However, little is known of the implementation process by key personnel. The purpose of the current study was to qualitatively explore elementary school teachers' experiences and perspectives on an inclusive education policy and practice for students with ASD. Participants were from 5 elementary schools in 2 districts in Shanghai. This study consisted of data collection in 2 phases. First, semi-structured, in-depth interviews were conducted with school psychologists and vice principals responsible for students' mental health for implementation of general inclusive education at each school. Second, focus groups of frontline teachers were assembled to hear their firsthand experiences. A thematic analysis was performed. Findings indicated that although all 5 schools had some ASD-related support, training and resources varied depending on whether learning in regular classrooms (LRC) was implemented. Frontline teachers in particular faced challenges implementing LRC, including the limited extent of LRC, tedious implementation procedures, and parents' misconceptions of LRC. Regardless of these challenges, frontline teachers tried to support students with ASD as much as they could. The current findings should help to advance the inclusive education policy in Shanghai, including increasing the availability of inclusive education resources and training for teachers, issuing specific LRC guidance, and reducing ASD-related stigma. This study is among the first to explore the implementation of inclusive education in urban China.

Millisecond-Range Time-Resolved Bioimaging Enabled through Ultralong Aqueous Phosphorescence Probes.

Probes featuring room-temperature phosphorescence (RTP) are promising tools for time-resolved imaging. It is worth noting that the time scale of time-resolved bioimaging generally ranges around the microsecond level, because of the short-lived emission. Herein, the first example of millisecond-range time-resolved bioimaging is illustrated, which is enabled through a kind of ultralong aqueous phosphorescence probes (i.e., cyclo-(Arg-Gly-AspD-Tyr-Cys)-conjugated zinc-doped silica nanospheres), with a RTP emission lasting for ≈5 s and a lifetime as long as 743.7 ms. We demonstrate that live cells and deep tumor tissue in mice can be specifically targeted through immune-phosphorescence imaging, with a high signal-to-background ratio (SBR) value of ≈69 for in vitro imaging, and ≈627 for in vivo imaging, respectively. We further show that, compared to that of fluorescence imaging, the SBR enhancement of millisecond-range time-resolved in vivo bioimaging is up to 105 times.

Nanoparticles as a Hedgehog signaling inhibitor for the suppression of cancer growth and metastasis.

Nanoparticles (NPs) have been intensively explored for the treatment of tumors during the past decade, yet little information has been provided on the NPs' inherent therapeutic activity against cancers. With this goal in mind, we reveal that biocompatible silicon (Si) NPs (SiNPs) feature excellent anti-growth and anti-metastasis activities against prostate cancer cells that show aberrant activation of the Hedgehog (HH) signaling pathway. Without activation by the Sonic hedgehog (Shh)-agonist, mouse embryonic fibroblast (NIH3T3) cells show no response to SiNP exposure. The distinct inhibitory effect of SiNPs on the HH signaling pathway leads to significant suppression of the proliferation, migration, and invasion of human prostate cancer cells. Crucially, in two mouse tumor models, the growth and metastasis of prostate cancer cells are also efficiently inhibited by SiNPs.

Targeted Noninvasive Treatment of Choroidal Neovascularization by Hybrid Cell-Membrane-Cloaked Biomimetic Nanoparticles.

Choroidal neovascularization (CNV) is the leading cause of vision loss in many blinding diseases, but current antiangiogenic therapies with invasively intravitreal injection suffer from poor patient compliance and a rate of devastating ocular complications. Here, we develop an alternative antiangiogenic agent based on hybrid cell-membrane-cloaked nanoparticles for noninvasively targeted treatment of CNV. The retinal endotheliocyte membrane coating provides as-fabricated nanoagents with homotypic targeting capability and binding ability to the vascular endothelial growth factor. The fusion of red blood cell membranes protects the hybrid membrane-coated nanoparticles from phagocytosis by macrophages. In a laser-induced wet age-related macular degeneration mouse model, a significantly enhanced accumulation is observed in CNV regions after intravenous delivery of the hybrid membrane-coated nanoparticles. Moreover, an excellent therapeutic efficacy is achieved in reducing the leakage and area of CNV. Overall, the biomimetic antiangiogenic nanoagents provide an effective approach for noninvasive treatment of CNV.

Hydrothermal Synthesis of Zinc-Doped Silica Nanospheres Simultaneously Featuring Stable Fluorescence and Long-Lived Room-Temperature Phosphorescence.

Fluorescence and phosphorescence are known as two kinds of fundamental optical signals, which have been used for myriad applications. To date, simultaneous activation of stable fluorescence and long-lived room-temperature phosphorescence (RTP) emission in the aqueous phase remains a big challenge. We prepare zinc-doped silica nanospheres (Zn@SiNSs) with fluorescence and RTP properties using a facile hydrothermal synthetic strategy. For the as-prepared Zn@SiNSs, the recombination of electrons and holes in defects and defect-stabilized excitons derived from oxygen vacancy/C=N bonds lead to the production of stable fluorescence and long-lived RTP (emission lasting for ≈9 s, quantum yield (QY): ≈33.6 %, RTP lifetime: ≈236 ms). The internal Si-O bonded networks and hydrophilic surface in Zn@SiNSs can reduce nonradiative decay to form self-protective RTP, and also provide high water solubility, excellent pH- and photostability.

[Clinical application of acellular dermal matrix to prevent gustatory sweating syndrome].

OBJECTIVE: To evaluate the clinical effect of acellular dermal matrix (ADM) on preventing Frey syndrome after parotidectomy. METHODS: Fifty-seven patients were randomized into two groups, ADM group (30 patients) receiving acellular dermal matrix and control group (27 patients) without application of acellular dermal matrix. The incidence of Frey syndrome was evaluated after operation. RESULTS: The incidences of Frey syndrome were 13.3% in ADM group and 55.6% in control group. There was significant difference in Frey syndrome incidence between the two groups (P < 0.01). CONCLUSIONS: The application of acellular dermal matrix could effectively prevent Frey syndrome after parotidectomy.