A cascaded MZI-coupled ring resonator (CMCR) optical sensor based on silicon nitride waveguide is proposed. The sensor is composed of a large size microring and a bus waveguide coupled with the ...microring for four times. The three-segment bus and the microring waveguide between the four coupling regions form three MZI of the same size, forming a three-stage cascaded MZI. The resonant effect of the cascaded MZI transforms the smooth comb spectrum of the microring into a V-shaped comb spectrum, expands the effective free spectral range of the ring resonator, and realizes the cascaded MZI-coupled microring sensor with a large measurement range. For the cascade MZI-coupled microring with a radius of 100μm, the effective free spectrum range is 53.7nm, which is more than 24 times larger than that of the all-pass microring of the same size. The refractive index sensitivity is 339.49 nm RIU/and the detection limit is 2.95 × 10
RIU. these excellent properties prove the feasibility of cascaded MZI-coupled microring structure for large measurement range sensing, and are expected to be used in large refractive index range sensing applications in the future.
Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges ...for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.
This work introduces a targeting drug delivery system (SPP-ARV-825) consisting of mPEG-PDLLA, SP-PEG-PDLLA and BRD4 PROTAC drug ARV-825 for glioma therapy. The SPP-ARV-825 efficiently induces BRD4 degradation and attenuates glioma tumor growth. The antitumor mechanisms of SPP-ARV-825 involve cells proliferation inhibition, apoptosis induction and M2 macrophages reduction. Display omitted
Lung cancer is the most common malignancy in the world, with a high mortality rate. Nevertheless, therapies to act effectively against lung cancer remain elusive. So far, chemotherapy is still the ...frontline treatment of lung cancer. Doxorubicin (DOX) is a broad-spectrum anti-tumor drug. However, DOX often has serious side effects and causes multi-drug resistance, which greatly limits its clinical application. In this work, biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) and cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) polypeptide modified PEG-PLA (cRGD-PEG-PLA) copolymers were used for the co-delivery of curcumin (CUR) and DOX (CUR-DOX/cRGD-M). The particle size of the self-assembled drug-loaded nanomicelle approximately was 27.4 nm and the zeta potential was −2.7 mV. Interestingly, CUR can enhance the uptake of DOX by Lewis lung carcinoma (LL/2) cells. The experimental results in vivo and in vitro showed that CUR-DOX/cRGD-M combination therapy could promote apoptosis of lung cancer cells, and conspicuously inhibit the tumor growth. Our data indicate that CUR-DOX/cRGD-M will be biodegradable and sustainable, which may have potential clinical application value in the treatment of lung cancer.
Self-assembled nanocomposites composed of MPEG-PLA polymer, cRGD-PEG-PLA polymer, curcumin (CUR) and doxorubicin (DOX) were injected intravenously into Lewis lung carcinoma (LL/2) tumor-bearing mice, which showed remarkable ability of promoting tumor apoptosis, inhibiting tumor proliferation and inhibiting tumor angiogenesis. Display omitted
Owing to the excellent antibacterial and antiviral activity, silver nanoparticles have a widespread use in the food and pharmaceutical industries. With the increase in the production and use of the ...related products, the potential hazard of silver nanoparticles has aroused public attention. The main purpose of this study is to explore the toxicity of silver nanoparticles and induction of lung inflammation in vitro and in vivo. Here, we validated that small amounts of silver ions dissolved from silver nanoparticles caused the depolarization of plasma membrane, resulting in an overload of intracellular sodium and calcium, and eventually led to the cell necrosis. The blockers of calcium or sodium channels inversed the toxicity of silver ions. Then, we instilled silver nanoparticles or silver nitrate (50 μg per mouse) into the lungs of mice, and this induced pulmonary injury and mitochondrial content release, led to the recruitment of neutrophils to the lung tissue via p38 MAPK pathway. Altogether, these data show that released silver ions from nanoparticles induced cell necrosis through Na
+
and Ca
2+
influx and triggered pulmonary inflammation through elevating mitochondrial-related contents released from these necrotic cells.
The temple gardens are an important human landscape and have an important position in the Chinese garden system. Using GIS analysis tools, primarily the Nearest Neighbor Index, Kernel Density ...Estimation, and Spatial Autocorrelation, and employing a Geographic Detector model, we analyzed the spatial distribution characteristics and influencing factors of 4,317 temples and gardens in Jiangxi Province. Research shows that: 1) The spatial distribution type of temple gardens in Jiangxi Province is agglomeration type, with large spatial differences in distribution, forming a spatial distribution pattern of “generally dispersed and concentrated in some areas”; 2) the distribution of temple gardens in Jiangxi Province is uneven. They are mostly distributed in five prefecture-level cities: Ganzhou, Jiujiang, Shangrao, Fuzhou, and Nanchang; 3) The overall spatial distribution of temple gardens in Jiangxi Province has positive autocorrelation characteristics, and prefecture-level cities have significant proximity characteristics, forming a “high-high” “agglomeration” and “low-low agglomeration” distribution patterns; 4) Temple gardens in various regions are affected by geomorphological factors, and are mostly concentrated in the lower altitude range of 0–500 m and the gentle slope of 0°–30°. Most of the distribution density of temple gardens in various prefecture-level cities is within the buffer zone distance of the road network within the range of 0–1.5 km. 5) Economic, cultural, demographic, and historical factors have affected the development of temple gardens. Areas with more active economies have a denser number of temple gardens. The unique regional culture affects the distribution of temples and gardens in different regions. In places where the modern population is densely distributed, there are fewer temples and gardens, while in places where the population is less densely distributed, there are more temples and gardens. 6) The use of geographical detectors to detect influencing factors shows that the greatest impact on the spatial distribution of temple gardens in Jiangxi Province is the road network, followed by elevation, slope, GDP, and water systems. The research is conducive to scientific understanding of the distribution of temple gardens among prefecture-level cities in Jiangxi Province, and provides reference for strengthening the protection of temple gardens and exploring the tourism characteristics of temple gardens.
As one of hydrofluoroolefins (HFOs), HFO-1336mzz(E) is regarded as a promising eco-friendly alternative insulation medium to Sulfur Hexafluoride (SF6) owing to its excellent environmental effect and ...insulation property. To study the decomposition mechanism and insulation stability, the decomposition experiment of a 0.5 MPa mixture containing 8% HFO-1336mzz(E) and 92% air was performed under AC breakdown conditions. The results indicated that the main decomposition products were CF4, C2F6, C3F8, CF3H, CF3C=CH, CF3CH=CHF(E), CF3CHF2, CF3CH=CH2, CF2=CFH, CF2=CH2, CH≡CH, C4H2F6O, CF3O3CF3, etc. Among them, the generation of C3F8, CH≡CH, and C4H2F6O was relatively more difficult than others. Thus, these three compounds can be considered typical decomposition products. New elements, namely C, F, and N, appeared on the electrode surface after breakdowns compared to the state before breakdowns. It can be concluded that some complex chemical reactions were triggered between the electrode material and gas mixture under the action of breakdown discharge. Additionally, the breakdown voltage of the HFO-1336mzz(E)/air mixture almost remained unchanged, showing that the gas mixture still exhibited an excellent insulation stability after multiple breakdowns.
Hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR) have been considered as two critical processes in the field of electrocatalytic water-splitting for hydrogen production and fuel ...cells. However, the sluggish reaction kinetics of HER and ORR required efficient electrocatalyst such as Pt to promote such process. Transition metal phosphides (TMPs) exhibit great potential to replace noble metal electrocatalysts to accelerate HER and ORR due to their high activity and easy availability. Herein, a highly-efficient bifunctional CoP electrocatalyst for HER and ORR, featuring a unique core-shell structure decorated on nitrogen-doped carbon matrix was designed and constructed via etching a cobalt-based zeolitic imidazolate framework (ZIF-67) with phytic acid (PA) followed by pyrolysis treatment (PA-ZIF-67–900). Experimental results revealed that the pure-phase single-crystalline CoP exhibited outstanding electrocatalytic performance in HER and ORR, superior to Co(PO3)2 in PA-ZIF-67–700, hybrid phase of Co(PO3)2 and CoP in PA-ZIF-67–800 and Co2P-doped CoP in PA-ZIF-67–1000. To reach the current density of 10 mA/cm2 the as-synthesized CoP required an overpotential of 120 mV for HER in 1 mol/L KOH and half-wave potential of 0.85 V in O2-saturated 0.1 mol/L KOH. This work present new clue for construction of efficient and bifunctional electrocatalyst in the field of energy conversion and storage
A phase-mediated cobalt phosphide with unique core-shell architecture was synthesized which could serve as efficient and bifunctional electrocatalyst for hydrogen evolution and oxygen reduction reaction. Display omitted
Conventional medical agents for oral squamous cell carcinoma (OSCC) with some adverse effects no longer meet the needs of the public. In this study, the prognosis-related hub genes of ...osmanthus-targeted therapy for OSCC were predicted and analyzed by network pharmacology and molecular docking. Osmanthus was extracted using the ethanol reflux method and osmanthus-loaded PVP/PVA (OF/PVP/PVA) hydrogel was prepared by electron beam radiation. The molecular structure, crystal structure and microscopic morphology of hydrogels were observed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. OSCC cells CAL-27 were cultured with OF/PVP/PVA hydrogel at different concentrations of extract to discover cell proliferation by MTT assay. The scratching test and JC-1 staining were used to observe the migration and mitochondrial membrane potential. Through experimental exploration, we found that a total of six prognosis-related targets were predicted, which are PYGL, AURKA, SQLE, etc., and osmanthus extract had good binding activity to AURKA. In vitro, except for proliferation inhibition, OF/PVP/PVA hydrogel prevented cell migration and changed the mitochondrial membrane potential of CAL-27 cells at a concentration equal to or greater than 50 μg/mL (p < 0.05). The addition of autophagy inhibitor chloroquine and 3-methyladenine weakened the migration inhibition of hydrogel (p < 0.05).
An urgently needed approach for the treatment of oral squamous cell carcinoma (OSCC) is the development of novel drug delivery systems that offer targeted specificity and minimal toxic side effects. ...In this study, we developed an injectable and temperature-sensitive composite hydrogel by combining mesoporous titanium dioxide nanoparticles (MTNs) with Poly(N-isopropylacrylamide) (PNIPAAM) hydrogel to serve as carriers for the model drug Astragalus polysaccharide (APS) using electron beam irradiation. The characteristics of MTNs, including specific surface area and pore size distribution, were analyzed, and the characteristics of MTNs-APS@Hyaluronic acid (HA), such as microscopic morphology, molecular structure, crystal structure, and loading efficiency, were examined. Additionally, the swelling ratio, gel fraction, and microscopic morphology of the composite hydrogel were observed. The in vitro cumulative release curve was plotted to investigate the sustained release of APS in the composite hydrogels. The effects on the proliferation, migration, and mitochondrial membrane potential of CAL-27 cells were evaluated using MTT assay, scratch test, and JC-1 staining. The results indicated successful preparation of MTNs with a specific surface area of 147.059 m2/g and an average pore diameter of 3.256 nm. The composite hydrogel displayed temperature-sensitive and porous characteristics, allowing for slow release of APS. Furthermore, it effectively suppressed CAL-27 cells proliferation, migration, and induced changes in mitochondrial membrane potential. The addition of autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) attenuated the migration inhibition (p < 0.05).
α-Mangostin (αM), a traditional natural product with promising application of treating a series of diseases, was limited use in clinical due to its hydrophobicity. Herein, MPEG-PCL nanomicelles were ...used to embed the αM for resolving hydrophobicity and improving the anti-melanoma effect of the αM. The anti-melanoma activity and potential mechanisms of biodegradable αM/MPEG-PCL nanomicelles were investigated. The αM/MPEG-PCL nanomicelles possessed a stronger effect on anti-melanoma compared to the free αM both in vitro and in vivo with a low cytotoxicity in non-tumor cell lines. In the research of mechanisms, the αM/MPEG-PCL nanomicelles inhibited the proliferation of melanoma cell, induced apoptosis via both apoptosis pathways of intrinsic and exogenous in vitro, as well as suppressed tumor growth and restrained angiogenesis in vivo, which implied that the αM/MPEG-PCL nanomicelles have potential application as a novel chemotherapeutic agent in melanoma therapy.