Traditional phototherapies face the issue that the insufficient penetration of light means it is difficult to reach deep lesions, which greatly reduces the feasibility of cancer therapy. Here, an ...implantable nitric oxide (NO)‐release device is developed to achieve long‐term, long‐distance, remote‐controllable gas therapy for cancer. The device consists of a wirelessly powered light‐emitting diode (wLED) and S‐nitrosoglutathione encapsulated with poly(dimethylsiloxane) (PDMS), obtaining the NO‐release wLED (NO‐wLED). It is found that NO release from the NO‐wLED can be triggered by wireless charging and the concentration of produced NO reaches 0.43 × 10−6 m min−1, which can achieve a killing effect on cancer cells. In vivo anticancer experiments exhibit obvious inhibitory effect on the growth of orthotopic cancer when the implanted NO‐wLED is irradiated by wireless charging. In addition, recurrence of cancer can be prevented by NO produced from the NO‐wLED after surgery. By illumination in the body, this strategy overcomes the poor penetration and long‐wavelength dependence of traditional phototherapies, which also provides a promising approach for in vivo gas therapy remote‐controlled by wireless charging.
An implantable and wirelessly charged nitric oxide (NO)‐release device (NO‐wLED) capable of being remote‐controlled is constructed to overcome the issue in that it is difficult to treat deep cancer by phototherapy due to the insufficient penetration capability of light. With irradiation in the body and the good tissue penetration of NO, suppression of orthotopic and postsurgery cancers is achieved.
Abstract
Objectives
To identify a novel plasmid-mediated colistin resistance gene in Klebsiella pneumoniae isolated from chickens in China.
Methods
WGS was used to identify a novel colistin ...resistance gene. The transferability of plasmids carrying mcr-7.1 was investigated by conjugation experiments. The expression of the mcr-7.1 gene was examined using an expression vector.
Results
A novel plasmid-mediated colistin resistance gene mcr-7.1, sharing 70% amino acid identity with the mcr-3 gene, was identified in three K. pneumoniae strains isolated from chickens in China. The mcr-7.1 gene was found in an IncI2-type plasmid (pSC20141012) that co-harboured the blaCTX-M-55 gene in one isolate. pSC20141012 can be transferred from K. pneumoniae SC20141012 to Escherichia coli J53Azr, exhibiting a ≥8-fold increase in colistin MIC compared with the recipient E. coli J53Azr.
Conclusions
We identified a novel plasmid-mediated colistin resistance gene named mcr-7.1 in K. pneumoniae in China. The prevalence of mcr-7.1 in various species of human and animal origin needs to be investigated immediately.
Highlights ► We successfully prepared hyaluronic acid coated, paclitaxel loaded, nanostructured lipid carriers (HA-NLCs) via electrostatic attraction. ► The in vitro cytotoxicity of HA-NLCs was ...superior to that of Taxol® in B16, CT26 and HCT116 cell lines. ► The in vivo antitumor effect of HA-NLCs in B16-bearing Kunming mice was extremely promising. ► HA-NLC prepared via electrostatic attraction was an effective carrier for delivering paclitaxel PTX to tumors overexpressing CD44.
Atomically dispersed metal‐nitrogen‐carbon (M‐N‐C) catalysts have exhibited encouraging oxygen reduction reaction (ORR) activity. Nevertheless, the insufficient long‐term stability remains a ...widespread concern owing to the inevitable 2‐electron byproducts, H2O2. Here, we construct Co‐N‐Cr cross‐interfacial electron bridges (CIEBs) via the interfacial electronic coupling between Cr2O3 and Co‐N‐C, breaking the activity‐stability trade‐off. The partially occupied Cr 3d‐orbitals of Co‐N‐Cr CIEBs induce the electron rearrangement of CoN4 sites, lowering the Co‐OOH* antibonding orbital occupancy and accelerating the adsorption of intermediates. Consequently, the Co‐N‐Cr CIEBs suppress the two‐electron ORR process and approach the apex of Sabatier volcano plot for four‐electron pathway simultaneously. As a proof‐of‐concept, the Co‐N‐Cr CIEBs is synthesized by the molten salt template method, exhibiting dominant 4‐electron selectively and extremely low H2O2 yield confirmed by Damjanovic kinetic analysis. The Co‐N‐Cr CIEBs demonstrates impressive bifunctional oxygen catalytic activity (▵E=0.70 V) and breakthrough durability including 100 % current retention after 10 h continuous operation and cycling performance over 1500 h for Zn‐air battery. The hybrid interfacial configuration and the understanding of the electronic coupling mechanism reported here could shed new light on the design of superdurable M‐N‐C catalysts.
A cross‐interfacial electronic bridges (CIEBs) is constructed via interfacial electronic coupling between Cr2O3 and Co‐N‐C, breaking the trade‐off between activity and stability. The partially occupied Cr 3d‐orbitals of Co‐N‐Cr CIEBs induce the electron rearrangement of CoN4 sites, lowering the Co‐OOH* antibonding orbital occupancy and accelerating the adsorption of intermediates. Consequently, the Co‐N‐Cr CIEBs suppress the two‐electron ORR process and approach the apex of Sabatier volcano plot for four‐electron pathway simultaneously.
Diamide resistant phenotypes have evolved in the field and the resistance has been attributed to target-site mutations in some lepidopteran pests. In this study, we documented the resistance status ...of Chilo suppressalis to chlorantraniliprole during 2016–2018 in seven provinces of China. To investigate the possible role of target-site mutations as known from lepidopterans, we sequenced respective domains of the RyR gene of C. suppressalis with different levels of diamide resistance. The results revealed that I4758M (corresponding to I4790M in P. xylostella), Y4667D/C (numbered according to C. suppressalis), G4915E (corresponding to G4946E in P. xylostella), and one novel Y4891F (numbered according to C. suppressalis) RyR target-site mutations were present. The contribution of these mutations was further investigated by diamide toxicity bioassays with eight genome modified Drosophila melanogaster lines. The study showed that genome modified flies bearing the Y4667D mutation (corresponding to the Y4667D and I4758M simultaneous mutation in C. suppressalis) exhibited high resistance ratios to chlorantraniliprole (1542.8-fold), cyantraniliprole (487.9-fold) and tetrachlorantraniliprole (290.1-fold). The M4758I and G4915E simultaneous mutations (corresponding to single G4915E mutation in C. suppressalis) showed high resistance ratios to chlorantraniliprole (153.1-fold) and cyantraniliprole (323.5-fold), and relatively low resistance to flubendiamide (28.9-fold) and tetrachlorantraniliprole (25.2-fold). These findings suggest that multiple point mutations in RyR confer diamide resistance of C. suppressalis. The results contribute to a better understanding of insect diamide resistance mechanisms and provide insights on the impact of RyR target-site mutations in insects.
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•Most of C. suppressalis field populations had developed high level of resistance to chlorantraniliprole.•Five mutations, I4758M, Y4667D, Y4667C, G4915E, and Y4891F are present in C. suppressalis populations.•Y4667D mutation confers very high resistance to chlorantraniliprole in Drosophila.•Double mutation, M4758I and G4915E, confers high chlorantraniliprole resistance in Drosophila.
Scope
Gallic acid (GA) is a dietary phenolic acid found in tea, red wine, and some plants. It exhibits anti‐oxidative and anti‐inflammatory activities. Recent studies have revealed that GA has ...beneficial effects against several cardiovascular diseases; however, whether GA attenuates pressure‐overload‐induced cardiac hypertrophy and the underlying mechanism remains unclear.
Methods and results
Primary cardiomyocyte hypertrophy is stimulated with angiotensin II (Ang II). Cardiac hypertrophic remodeling is induced in mice by transverse aortic constriction (TAC). Myocardial function is evaluated by echocardiographic and hemodynamic analyses, while cardiac tissues are analyzed by histological staining. It is observed that GA significantly decreases Ang II‐induced increases in cardiomyocyte size in vitro. Administration of GA in mice markedly improves TAC‐induced cardiac dysfunction and attenuates pathological changes, including cardiac myocyte hypertrophy, fibrosis, inflammation, and oxidative stress. Mechanistically, GA inhibits ULK1 and activates autophagy, which induces the degradation of EGFR, gp130, and calcineurin A, thereby inhibiting the downstream signaling cascades (AKT, ERK1/2, JAK2/STAT3, and NFATc1).
Conclusions
The results demonstrate for the first time that GA prevents myocardial hypertrophy and dysfunction via an autophagy‐dependent mechanism. Thus, GA represents a promising therapeutic candidate for treating cardiac hypertrophy and heart failure.
Gallic acid (GA), a type of dietary phenolic acid found in tea and other plants, prevents angiotensin II‐induced cardiomyocyte hypertrophy and pressure overload‐induced myocardial dysfunction. Mechanistically, GA enhances autophagy activation which promotes degradation of epidermal growth factor receptor, glycoprotein 130 and calcineurin A resulting in inhibition of downstream signaling cascades.
Cancer cells, with unique their metabolism, frequently exhibit a high level of redox homeostasis, which could be a feasible target for cancer treatment. Here, liquid metal (LM) nanoparticles are used ...as a template to guide the growth of yolk‐shell structured LM@MnO2 (LMN). With yolk‐shell structures, LMNs is applied to load with cinnamaldehyde (CA) (CLMN) and further coated with hyaluronic acid (HA) to construct the CA&LM@MnO2‐HA nanoflowers (CLMNF) for cancer targeted treatment. Owing to the urchin‐like structured shell, it is found that the obtained CLMNF particles rapidly deplete glutathione (GSH) and produce manganese ions, which further facilitate hydrogen peroxide converting into hydroxyl radical (·OH) for cancer cell killing. Accompanying the depletion of GSH, the balance of intracellular redox homeostasis tilts towards oxidation, resulting in amplified oxidative damage caused by CA, eventually, leading to the apoptosis of cancer cells. Combined with the remarkable near infrared (NIR) photothermal conversion properties, the novel structured CLMNF exhibits favorable inhibition of tumors in vivo, indicating that using nanoflowers to induce intracellular oxidative/thermal stress damage could be a promising strategy for anticancer treatment.
Yolk‐shell structured nanoflowers induce intracellular oxidative/thermal stress damage for cancer treatment. By using liquid metal as a template, the yolk‐shell structured manganese dioxide nanoflowers are rapidly constructed through an in situ surface reduction process. Benefiting from the guidance of multimode imaging, the nanoparticles exhibit satisfactory inhibition of tumor growth in vivo.
Herein, we report a Rh(III)‐catalyzed 1,3‐dienylation of isoquinolin‐1(2H)‐ones through C−H activation. The present reaction enables the preparation of 3‐(buta‐1,3‐dien‐2‐yl)isoquinolin‐1(2H)‐ones ...through the direct cross‐coupling reaction of readily available isoquinolin‐1(2H)‐ones with methylenecyclopropanes, while tolerating many sensitive functional groups. Therefore, this method provides an efficient and convenient approach for modification of interesting molecules.
Angiotensin II stimulates fibroblast proliferation and substantially alters gene expression patterns leading to cardiac remodeling, but the mechanisms for such differences are unknown. MicroRNAs are ...a novel mechanism for gene expression regulation. Herein, we tested the miRNA and mRNA expression patterns in mouse heart using microarray assay and investigated their role in angiotensin II-induced cardiac remodeling. We found that let-7i was dynamically downregulated in angiotensin II-infused heart at day 3 and 7 and had the most targets that were mainly associated with cardiac inflammation and fibrosis. Overexpression or knockdown of let-7i in cultured cardiac fibroblasts demonstrated that let-7i played an inhibitory effect on the expression of its targets interleukin-6 and collagens. Furthermore, delivery of let-7i to mouse significantly inhibited angiotensin II-induced cardiac inflammation and fibrosis in a dose-dependent manner. Conversely, knockdown of let-7i aggravated this effect. Together, our results clearly demonstrate that let-7i acts as a novel negative regulator of angiotensin II-induced cardiac inflammation and fibrosis by suppressing the expression of interleukin-6 and multiple collagens in the heart and may represent a new potential therapeutic target for treating hypertensive cardiac fibrosis.
No consensus was reached on the efficacy of postoperative radiotherapy (PORT) in locally invasive thymomas because of the rarity of the thymic epithelial and the variations of study results. ...Therefore, we aimed to explore the efficacy of PORT in locally invasive thymomas using the Surveillance, Epidemiology, and End Results (SEER) database.
Patients diagnosed with thymomas from 2004 to 2016 were identified using the SEER database. Prognostic factors of cancer-specific survival (CSS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses.Propensity score matching (PSM) was performed to balance the baseline characteristics.
A total of 700 eligible patients were identified. After PSM, 262 paired patients were selected from the two groups, those who received or did not receive PORT. Receiving PORT improved CSS and OS before and after PSM. In the matched population, the multivariate analyses showed that tumour invasion into adjacent organs/structures and non-utilisation of PORT were independent poor prognostic factors for CSS, whereas age ≥62 years,tumour invasion into adjacent organs/structures, and non-utilisation of PORT were independently associated with poorer OS. The subgroup analysis revealed that PORT improved CSS and OS in Masaoka-Koga stage III thymoma, but showed no OS benefit in Masaoka-Koga stage IIB thymoma.
Based on the SEER database, we found that PORT provides a significant survival benefit in Masaoka-Koga stage III thymoma with complete or incomplete resection. The role of PORT in thymoma requires further evaluation.
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