Considering that hypoxia is closely associated with tumor proliferation, invasion, metastasis, and drug resistance, it is of great significance to overcome hypoxia in tumor treatment. Herein, we ...report a hypoxia-induced specific photothermal therapy (PTT) based on the photothermal agent of supramolecular perylene diimide radical anions. Hypoxic regions in various tumors display strong reductive ability, and in such environments the supramolecular complex of a perylene diimide derivative and cucurbit7uril could be reduced to supramolecular perylene diimide radical anions. Benefiting from the strong NIR absorption and good photothermal conversion performance of the in situ generated supramolecular perylene diimide radical anions, the hypoxia-induced PTT strategy exhibits excellent photothermal therapeutic efficiency as well as good specificity and biological safety. Moreover, hypoxia inducible factor expression of tumors decreases to the normal level after PTT treatment. It is anticipated that such a hypoxia-induced specific PTT strategy opens new horizons for photothermal therapy against hypoxic tumors with improved specificity and safety.
A central neural circuit for itch sensation Mu, Di; Deng, Juan; Liu, Ke-Fei ...
Science (American Association for the Advancement of Science),
08/2017, Letnik:
357, Številka:
6352
Journal Article
Recenzirano
Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. ...However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.
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•Nanostructured TiO2/activated carbon fiber felt porous composites are prepared.•Nanostructures TiO2 particles on fibers are constructed by nanocrystals.•They have synergetic ...adsorption-photocatalytic activities for toluene removal.•The adsorption efficiency reaches 98% at toluene concentrations <1150ppm.•Carbon fibers can hinder the recombination of electron-hole pairs on TiO2.
The low quantum efficiency and limited adsorption efficiency of TiO2 makes it only fit for the removal of VOCs with low concentrations. Herein, we for the first time fabricated nanostructured TiO2/activated carbon fiber felt (TiO2/ACFF) porous composites by the in situ deposition of TiO2 microspheres on the carbon fibers in ACFF. Interestingly, the TiO2 microspheres exhibit hierarchical nanostructures constructed by nanocrystals as building blocks. The TiO2/ACFF porous composites possess excellent adsorption and photodegradation properties for toluene because of the synergetic effects between the nanostructured TiO2 and ACFF. The adsorption efficiencies of the TiO2/ACFF porous composites reach approximately 98% at the toluene concentration (<1150ppm) and approximately 77% even at the high concentration of 6900ppm. Moreover, the ACFF in the TiO2/ACFF porous composites significantly enhances photocatalytic property for toluene by hindering the recombination of electron-hole pairs, reducing the TiO2 band gap energy (Eg) to 2.95eV and accelerating toluene adsorption. At the toluene concentrations of 230ppm and 460ppm, the photocatalytic oxidation efficiency of toluene into CO2 arrives at 100% and 81.5%, respectively. Therefore, the TiO2/ACFF porous composites with synergetic adsorption and photocatalytic activities have great potentials for toluene removal.
Predicting the number of new suspected or confirmed cases of novel coronavirus disease 2019 (COVID-19) is crucial in the prevention and control of the COVID-19 outbreak. Social media search indexes ...(SMSI) for dry cough, fever, chest distress, coronavirus, and pneumonia were collected from 31 December 2019 to 9 February 2020. The new suspected cases of COVID-19 data were collected from 20 January 2020 to 9 February 2020. We used the lagged series of SMSI to predict new suspected COVID-19 case numbers during this period. To avoid overfitting, five methods, namely subset selection, forward selection, lasso regression, ridge regression, and elastic net, were used to estimate coefficients. We selected the optimal method to predict new suspected COVID-19 case numbers from 20 January 2020 to 9 February 2020. We further validated the optimal method for new confirmed cases of COVID-19 from 31 December 2019 to 17 February 2020. The new suspected COVID-19 case numbers correlated significantly with the lagged series of SMSI. SMSI could be detected 6-9 days earlier than new suspected cases of COVID-19. The optimal method was the subset selection method, which had the lowest estimation error and a moderate number of predictors. The subset selection method also significantly correlated with the new confirmed COVID-19 cases after validation. SMSI findings on lag day 10 were significantly correlated with new confirmed COVID-19 cases. SMSI could be a significant predictor of the number of COVID-19 infections. SMSI could be an effective early predictor, which would enable governments' health departments to locate potential and high-risk outbreak areas.
Nucleolus, which participates in many crucial cellular activities, is an ideal target for evaluating the state of a cell or an organism. Here, bright red‐emissive carbon dots (termed CPCDs) with ...excitation‐independent/polarity‐dependent fluorescence emission are synthesized by a one‐step hydrothermal reaction between congo red and p‐phenylenediamine. The CPCDs can achieve wash‐free, real‐time, long‐term, and high‐quality nucleolus imaging in live cells, as well as in vivo imaging of two common model animals—zebrafish and Caenorhabditis elegans (C. elegans). Strikingly, CPCDs realize the nucleolus imaging of organs/flowing blood cells in zebrafish at a cellular level for the first time, and the superb nucleolus imaging of C. elegans suggests that the germ cells in the spermatheca probably have no intact nuclei. These previously unachieved imaging results of the cells/tissues/organs may guide the zebrafish‐related studies and benefit the research of C. elegans development. More importantly, a novel strategy based on CPCDs for in vivo toxicity evaluation of materials/drugs (e.g., Ag+), which can visualize the otherwise unseen injuries in zebrafish, is developed. In conclusion, the CPCDs represent a robust tool for visualizing the structures and dynamic behaviors of live zebrafish and C. elegans, and may find important applications in cell biology and toxicology.
Red‐emissive carbon dots (termed CPCDs) with excitation‐independent/polarity‐dependent fluorescence emission are prepared. The CPCDs can realize wash‐free, real‐time, long‐term (24 h), and high‐quality nucleolus imaging of two model animals—zebrafish and Caenorhabditis elegans. In addition, CPCDs are adopted for successfully visualizing the detailed damage in zebrafish caused by a model drug—silver ion (Ag+).
There is a need to find better strategies to promote wound healing, especially of chronic wounds, which remain a challenge. We found that synovium mesenchymal stem cells (SMSCs) have the ability to ...strongly promote cell proliferation of fibroblasts; however, they are ineffective at promoting angiogenesis. Using gene overexpression technology, we overexpressed microRNA‐126‐3p (miR‐126‐3p) and transferred the angiogenic ability of endothelial progenitor cells to SMSCs, promoting angiogenesis. We tested a therapeutic strategy involving controlled‐release exosomes derived from miR‐126‐3p‐overexpressing SMSCs combined with chitosan. Our in vitro results showed that exosomes derived from miR‐126‐3p‐overexpressing SMSCs (SMSC‐126‐Exos) stimulated the proliferation of human dermal fibroblasts and human dermal microvascular endothelial cells (HMEC‐1) in a dose‐dependent manner. Furthermore, SMSC‐126‐Exos also promoted migration and tube formation of HMEC‐1. Testing this system in a diabetic rat model, we found that this approach resulted in accelerated re‐epithelialization, activated angiogenesis, and promotion of collagen maturity in vivo. These data provide the first evidence of the potential of SMSC‐126‐Exos in treating cutaneous wounds and indicate that modifying the cells—for example, by gene overexpression—and using the exosomes derived from these modified cells provides a potential drug delivery system and could have infinite possibilities for future therapy. Stem Cells Translational Medicine 2017;6:736–747
Green tea catechins have received significant attention due to their potent antioxidant activity as well as diverse biological properties. Stabilizing and protecting catechins from degradation is ...very important but challenging. In this work, a nanosized edible
γ
-cyclodextrin-based metal–organic framework (CD-MOF) was designed and fabricated by a facile vapor diffusion route and applied for the encapsulation of a model green tea catechin, (-)-epigallocatechin gallate (EGCG) for the first time. Downsizing CD-MOF to the nanoscale is a suitable method to tackle down new applications. Significantly, the antioxidant activity results show that the CD-MOF-EGCG can remarkably enhance the antioxidant activity in alkaline solutions, as compared to that of free EGCG. Furthermore, the prepared CD-MOF-EGCG showed strong cancer cell growth inhibitory effects on C6 cells as confirmed by the cell viability assay. This work demonstrates that such safe and nontoxic nanoscale CD-MOF-based porous materials hold great promise for applications in the field of stabilization of catechins for biomedical applications.
The prognostic value and clinical relevance of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA) remain unclear. Thus, we aimed to investigate the prognostic value and ...functional involvement of TLSs in iCCA.
We retrospectively included 962 patients from 3 cancer centers across China. The TLSs at different anatomic subregions were quantified and correlated with overall survival (OS) by Cox regression and Kaplan-Meier analyses. Multiplex immunohistochemistry (mIHC) was applied to characterize the composition of TLSs in 39 iCCA samples.
A quaternary TLS scoring system was established for the intra-tumor region (T score) and peri-tumor region (P score) respectively. T scores positively correlated with favorable prognosis (p <0.001), whereas a high P score signified worse survival (p <0.001). mIHC demonstrated that both T follicular helper and regulatory T cells were significantly increased in intra-tumoral TLSs compared to peri-tumoral counterparts (p <0.05), and regulatory T cell frequencies within intra-tumoral TLSs were positively associated with P score (p <0.05) rather than T score. Collectively, the combination of T and P scores stratified iCCAs into 4 immune classes with distinct prognoses (p <0.001) that differed in the abundance and distribution pattern of TLSs. Patients displaying an immune-active pattern had the lowest risk, with 5-year OS rates of 68.8%, whereas only 3.4% of patients with an immune-excluded pattern survived at 5 years (p <0.001). The C-index of the immune class was statistically higher than the TNM staging system (0.73 vs. 0.63, p <0.001). These results were validated in an internal and 2 external cohorts.
The spatial distribution and abundance of TLSs significantly correlated with prognosis and provided a useful immune classification for iCCA. T follicular helper and regulatory T cells may play a critical role in determining the functional orientation of spatially different TLSs.
Tertiary lymphoid structures (TLSs) are associated with favorable prognosis in a number of cancers. However, their role in intrahepatic cholangiocarcinoma (iCCA) remains unclear. Herein, we comprehensively evaluated the spatial distribution, abundance, and cellular composition of TLSs in iCCA, and revealed the opposite prognostic impacts of TLSs located within or outside the tumor. This difference could be mediated by the different immune cell subsets present within the spatially distinct TLSs. Based on our analysis, we were able to stratify iCCAs into 4 immune subclasses associated with varying prognoses.
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•Tertiary lymphoid structures (TLSs) within and outside the tumor have opposite prognostic impacts on patients with iCCA.•The heterogeneous distribution of Tfh and Treg cells within distinct TLSs might be a determinant of their functional state.•The geographic integration of TLSs stratified iCCAs into 4 immune subclasses with distinct clinical outcomes.
The purpose of this research was to evaluate the efficacy of 3 ovulation induction therapies for treating infertility in patients with polycystic ovary syndrome (PCOS). In this retrospective study, ...we compared the success rates of 90 patients who underwent intrauterine insemination, who were randomly assigned to 1 of 3 treatment groups: letrozole (LE) + urinary gonadotropin (human menopausal gonadotropin HMG), clomiphene (CC) + HMG, or HMG alone. Using ultrasound scanning, we examined the number of mature follicles, ovulation rate, clinical pregnancy rate, endometrial thickness, and blood flow. When compared to the other 2 groups, the LE + HMG group had significantly higher levels of mature follicles, ovulation rate, clinical pregnancy rate, estradiol, and luteinizing hormone on the day of the human chorionic gonadotropin injection and endometrial receptivity (P < .05). There was no statistically significant difference between the 3 groups in terms of abortion rate, ectopic pregnancy rate, or adverse reactions. In this research, we found that infertility in patients with PCOS could be effectively treated by combining LE with HMG. This protocol increased ovulation, boosted fertility, and enhanced endometrial receptivity with no increase in adverse reactions. Therefore, it may be a useful clinical approach for inducing ovulation and treating infertility in patients with PCOS.
Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II–IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with ...EGFR-mutant stage IB–IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II–IIIA (N1–N2) NSCLC.
We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18–75 years with completely resected (R0), stage II–IIIA (N1–N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079.
Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8–44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months 95% CI 24·9–32·5) than with vinorelbine plus cisplatin (18·0 months 13·6–22·3; hazard ratio HR 0·60, 95% CI 0·42–0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two 2% patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 34% patients vs none with gefitinib), leucopenia (14 16% vs none), and vomiting (eight 9% vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related.
Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II–IIIA (N1–N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature.
Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.
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