Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

A continuously efficient O2-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy.

Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H2O2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H2O2 into O2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients.

Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4 : 15 %Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

Hierarchically Organized Cocrystal of Tetra-Anionic Porphyrin and Di-Cationic Viologen: Ion Conformations, Supramolecule Interactions, and Porphyrin Arrays.

Ionic co-assembly of tetra-anionic porphyrins has been extensively researched in the construction of hierarchically organized architectures with potential application value in organic semiconductors, sunlight catalysts and supramolecular chirality systems. However, such architectures are difficult to grow to a size suitable for single-crystal X-ray diffraction (SCXRD); the lack of single-crystal structures of these architectures leads to challenges in gaining deeper comprehension about that. This study reports a hierarchically organized cocrystal of meso-tetra(4-sulfonato-phenyl)-porphyrin (TSPP4- ) and N, N'-diethyl-viologen (DEV2+ ), wherein wave-like and saddle-like TSPP4- ions co-aggregate at a stoichiometric ratio of 1 : 2 to form unique porphyrin arrays; the spectrum characteristics and calculated coulombic exciton coupling energy show that these porphyrin arrays are J-aggregates. We prove that the distortion of porphyrin ring of TSPP4- strongly correlates with the deflection of its phenyl groups. The crystal comprises six different ionic conformations, and the multiplicity of ionic conformation leads to intricate supramolecular interactions.

NIR-II Ratiometric Lanthanide-Dye Hybrid Nanoprobes Doped Bioscaffolds for In Situ Bone Repair Monitoring.

In situ monitoring of tissue regeneration progression is of primary importance to basic medical research and clinical transformation. Despite significant progress in the field of tissue engineering and regenerative medicine, few technologies have been established to in situ inspect the regenerative process. Here, we present an integrated second near-infrared (NIR-II, 1000-1700 nm) window in vivo imaging strategy based on 3D-printed bioactive glass scaffolds doped with NIR-II ratiometric lanthanide-dye hybrid nanoprobes, allowing for in situ monitoring of the early inflammation, angiogenesis, and implant degradation during mouse skull repair. The functional bioactive glass scaffolds contribute to more effective bone regeneration because of their excellent angiogenic and osteogenic activities. The reliability of ratiometric fluorescence imaging, coupled with low autofluoresence in the NIR-II window, facilitates the accuracy of in vivo inflammation detection and high-resolution visualization of neovascularization and implant degradation in deep tissue.

Breeding of ZhongKeFaZaoGeng1 by molecular design.

Double-cropping early-season rice is one important part of staple crop rice. In recent years, great progress has been made in breeding the double-cropping early-season japonica rice variety, ZhongKeFaZaoGeng1 (ZKFZG1), with high yield, good quality, and high resistance. The breeding of ZKFZG1 aimed at the severe problems of low quality, low income and pre-harvest sprouting in double-cropping early-season rice production, and was achieved through molecular design by selecting three parents with different beneficial genes, KongYu131, NanFangChangLiGeng, and JiGeng88 and screening for key agronomic genes in cross-breeding. ZKFZG1 has a compact plant architecture, a plant height of ~90 cm, a number of ~120 grains per panicle, a setting rate of ~85%, a 1000-grain weight of 26 grams, a yield of 8.25 t/ha, and especially good grain quality. The successful breeding of ZKFZG1 provides a new direction for double-cropping early-season rice production.

[Myrislignan Induces Apoptosis in Gastric Cancer Cell Line Through PI3K/AKT Signaling Pathway].

Objective: To investigate the effect of myrislignan (MYR) on the apoptosis of gastric cancer cell line and its relationship with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods: The gastric cells (SGC-7901) were treated with MYR at different concentrations, i.e., 0, 25, 50, 100, and 200 µmol/L, for 48 h and 72 h and the effect of MYR on the proliferation of SGC-7901 cells was measured by CCK-8 assay. Then, SGC-7901 cells were treated with different concentrations of MYR at 50, 100, and 200 µmol/L for 48 h. Meanwhile, a normal control group and a dimethyl sulfoxide (DMSO) solvent control group (0.1% DMSO) were established. Flow cytometry was used to determine the apoptosis rate of SGC-7901 cells. The protein expression levels of PI3K, AKT, Bcl-2-associated X protein (BAX), cysteine-dependent aspartate-specifc protease-3 (Caspase-3), and Caspase-9 were determined by Western blot. Then, PI3K activator (20 µmol/mL) was used to treat SGC-7901 cells for 48 h in 4 groups, the control group, 0.1% DMSO group, MYR group, and MYR+PI3K activator group, and the effect on MYR's induction of apoptosis and regulation of the protein expression levels of PI3K, AKT, BAX, Caspase-3, and Caspase-9 in SGC-7901 cells. Results: Compared with the control group, MYR at 50, 100 and 200 µmol/L inhibited the proliferation of gastric cancer cells, increased the apoptosis rate, down-regulated the protein expression levels of PI3K and AKT, and up-regulated the protein expression levels of BAX, Caspase-3, and Caspase-9 in a dose-dependent manner ( P<0.05). However, PI3K activator attenuated MYR-induced apoptosis in gastric cancer cells and MYR's regulation of PI3K, AKT, BAX, Caspase-3, and Caspase-9 protein expression ( P<0.05). Conclusion: MYR induces the expression of BAX, Caspase-3, and Caspase-9 proteins by inhibiting the PI3K/AKT signaling pathway, thereby promoting the apoptosis of gastric cancer cells.

An Extended NIR-II Superior Imaging Window from 1500 to 1900†nm for High-Resolution In Vivo Multiplexed Imaging Based on Lanthanide Nanocrystals.

High-resolution in vivo optical multiplexing in second near-infrared window (NIR-II, 1000-1700 nm) is vital to biomedical research. Presently, limited by bio-tissue scattering, only luminescent probes located at NIR-IIb (1500-1700 nm) window can provide high-resolution in vivo multiplexed imaging. However, the number of available luminescent probes in this narrow NIR-IIb region is limited, which hampers the available multiplexed channels of in vivo imaging. To overcome the above challenges, through theoretical simulation we expanded the conventional NIR-IIb window to NIR-II long-wavelength (NIR-II-L, 1500-1900 nm) window on the basis of photon-scattering and water-absorption. We developed a series of novel lanthanide luminescent nanoprobes with emission wavelengths from 1852 nm to 2842 nm. NIR-II-L nanoprobes enabled high-resolution in vivo dynamic multiplexed imaging on blood vessels and intestines, and provided multi-channels imaging on lymph tubes, tumors and intestines. The proposed NIR-II-L probes without mutual interference are powerful tools for high-contrast in vivo multiplexed detection, which holds promise for revealing physiological process in living body.

Effect of oxygen partial pressure on the performance of homojunction amorphous In-Ga-Zn-O thin-film transistors.

In this study, the homojunction thin-film transistors (TFTs) with amorphous indium gallium zinc oxide (a-IGZO) as active channel layers and source/drain electrodes were fabricated by RF magnetron sputtering. The effect of oxygen partial pressure on the phase, microstructure, optical and electrical properties of IGZO thin films was investigated. The results showed that amorphous IGZO thin films always exhibit a high transmittance above 90% and wide band gaps of around 3.9 eV. The resistivity increases as the IGZO thin films are deposited at a higher oxygen partial pressure due to the depletion of oxygen vacancies. In addition, the electrical behaviors in homojunction IGZO TFTs were analyzed. When the active channel layers were deposited with an oxygen partial pressure of 1.96%, the homojunction IGZO TFTs exhibited optimal transfer and output characteristics with a field-effect mobility of 13.68 cm2V-1s-1. Its sub-threshold swing, threshold voltage and on/off ratio are 0.6 V/decade, 0.61 V and 107, respectively.

Green Tides in the Yellow Sea Promoted the Proliferation of Pelagophyte Aureococcus anophagefferens.

Harmful algal blooms formed by fast-growing, ephemeral macroalgae have expanded worldwide, yet there is limited knowledge of their potential ecological consequences. Here, we select intense green tides formed by Ulva prolifera in the Yellow Sea, China, to examine the ecological consequences of these blooms. Using 28-isofucosterol in the surface sediment as a biomarker of green algae, we identified the settlement region of massive floating green algae in the area southeast of the Shandong Peninsula in the southern Yellow Sea. The responses of the phytoplankton assemblage from the deep chlorophyll-a maximum layer were then resolved using high-throughput sequencing. We found striking changes in the phytoplankton community in the settlement region after an intensive green tide in 2016, characterized by a remarkable increase in the abundance of the pelagophyte Aureococcus anophagefferens, the causative species of ecosystem disruptive brown tides. Our study strongly suggests that the occurrence of massive macroalgal blooms may promote blooms of specific groups of microalgae through alteration of the marine environment.

Chalcone derivatives ameliorate lipopolysaccharide-induced acute lung injury and inflammation by targeting MD2.

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are known as the common causes of respiratory failure in critically ill patients. Myeloid differentiation 2 (MD2), a co-receptor of toll like receptor 4 (TLR4), plays an important role in LPS-induced ALI in mice. Since MD2 inhibition by pharmacological inhibitors or gene knockout significantly attenuates ALI in animal models, MD2 has become an attractive target for the treatment of ALI. In this study we identified two chalcone-derived compounds, 7w and 7x, as new MD2 inhibitors, and investigated the therapeutic effects of 7x and 7w in LPS-induced ALI mouse model. In molecular docking analysis we found that 7w and 7x, formed pi-pi stacking interactions with Phe151 residue of the MD2 protein. The direct binding was confirmed by surface plasmon resonance analysis (with KD value of 96.2 and 31.2 µM, respectively) and by bis-ANS displacement assay. 7w and 7x (2.5, 10 µM) also dose-dependently inhibited the interaction between lipopolysaccharide (LPS) and rhMD2 and LPS-MD2-TLR4 complex formation. In mouse peritoneal macrophages, 7w and 7x (1.25-10 µM) dose-dependently inhibited LPS-induced inflammatory responses, MAPKs (JNK, ERK and P38) phosphorylation as well as NF-κB activation. Finally, oral administration of 7w or 7x (10 mg ·kg-1 per day, for 7 days prior LPS challenge) in ALI mouse model significantly alleviated LPS-induced lung injury, pulmonary edema, lung permeability, inflammatory cells infiltration, inflammatory cytokines expression and MD2/TLR4 complex formation. In summary, we identify 7w and 7x as new MD2 inhibitors to inhibit inflammatory response both in vitro and in vivo, proving the therapeutic potential of 7w and 7x for ALI and inflammatory diseases.

[Therapeutic Effect of Artesunate on Influenza A Viral Pneumonia].

Objective: To investigate the therapeutic effect of artesunate (ART) on influenza A viral pneumonia. Methods: A total of 36 mice were evenly and randomly assigned to six groups, a normal control group (C group), a solvent control group (M group, 10% DMSO), a positive drug group (P group, oseltamivir, 1.25 mg/kg/day), ART high-dose group (ART-G group, 120 mg/kg/day), ART medium-dose group (ART-Z group, 60 mg/kg/day), and ART low-dose group (ART-D group, 30 mg/kg/day). Except for group C, which did not receive any influenza A virus intervention or intraperitoneal injection, mice in the five other groups were infected with influenza A virus through intranasal drip. Then, after 12 hours, mice in the five other groups received intraperitoneal injection of the assigned drugs and dosage once a day. The signs, body weight, and survival of the mice were observed over the course of treatment. After 7 days of treatment, the lung tissue of the mice was collected and weighed, and the lung index was calculated accordingly. HE staining was performed to observe the pathological changes in the lung tissue. The mRNA and protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB [p65]), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-1ß were examined with RT-qPCR and Western blot, respectively. Results: Compared with those in C group, mice in the M group had worse physical signs and lower body mass and survival, increased lung index, severe pathological changes in lung tissue, and increased levels of TLR4, NF-κB (p65), TNF-α, IL-6 and IL-1ß mRNA and protein expression in their lung tissue ( P<0.05). Compared with those in M group, the mice in the ART groups had better physical signs, higher body mass and survival rate, decreased lung index, improvement of pathological changes in the lung tissue, and decreased levels of level of TLR4, NF-κB (p65), TNF-α, IL-6 and IL-1ß mRNA and protein expression in the lung tissue ( P<0.05). Furthermore, the most prominent changes in these indexes were observed in the ART-G group. Conclusion: ART has therapeutic effects on influenza A viral pneumonia, and the mechanisms are related to the inhibition of TLR4/p65 signaling pathway activation and anti-inflammation.

[Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis].

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.

A LRET Nanoplatform Consisting of Lanthanide and Amorphous Manganese Oxide for NIR-II Luminescence Lifetime Imaging of Tumor Redox Status.

Designing luminescence lifetime sensors in the second near-infrared (NIR-II) window is a great challenge due to the difficult structural construction. Here, we report a tumor redox responsive and easily synthesized material, amorphous manganese oxide (MnOx ) with indirect band gap of 1.02 eV, as an energy acceptor to build a luminescence resonance energy transfer (LRET) toolbox for universally regulating NIR-I to NIR-II luminescence lifetimes of lanthanide nanoparticles, in which energy transfer is based on matched energy gap instead of conventional overlapped spectra. We further utilize ytterbium (Yb3+ )-doped YbNP@MnOx as an NIR-II luminescence lifetime sensor to realize in vitro quantitative redox visualization with relative errors under 5 % in samples covered with mouse skin. Furthermore, HepG2 cells and tumors with high redox state have been accurately distinguished by NIR-II luminescence lifetime imaging. The quantified intracellular and intratumor glutathione (GSH) levels are highly consistent with the commercial kit results, illustrating the reliable redox visualization ability in biological tissue.

A Novel Cascade Nanoreactor Integrating Two-Dimensional Pd-Ru Nanozyme, Uricase and Red Blood Cell Membrane for Highly Efficient Hyperuricemia Treatment.

Nanozyme-based cascade reaction has emerged as an effective strategy for disease treatment because of its high efficiency and low side effects. Herein, a new and highly active two-dimensional Pd-Ru nanozyme is prepared and then integrated with uricase and red blood cell (RBC) membrane to fabricate a tandem nanoreactor, Pd-Ru/Uricase@RBC, for hyperuricemia treatment. The designed Pd-Ru/Uricase@RBC nanoreactor displayed not only good stability against extreme pH, temperature and proteolytic degradation, but also long circulation half-life and excellent safety. The nanoreactor can effectively degrade UA by uricase to allantoin and H2 O2 and remove H2 O2 by using Pd-Ru nanosheets (NSs) with the catalase (CAT)-like activity. More importantly, the finally produced O2 from H2 O2 decomposition can in turn facilitate the catalytic oxidation of UA, as the degradation of UA is an O2 consumption process. By integrating the high-efficiency enzymatic activity, long circulation capability, and good biocompatibility, the designed Pd-Ru/Uricase@RBC can effectively and safely treat hyperuricemia without side effects. The study affords a new alternative for the exploration of clinical treatment of hyperuricemia.

Effects of starvation and refeeding on growth performance, appetite, growth hormone-insulin-like growth factor axis levels and digestive function of Acipenser dabryanus.

The aim of this study was to explore the effects and mechanisms of different starvation treatments on the compensatory growth of Acipenser dabryanus. A total of 120 fish (60·532 (sem 0·284) g) were randomly assigned to four groups (fasting 0, 3, 7 or 14 d and then refed for 14 d). During fasting, middle body weight decreased significantly with prolonged starvation. The whole-body and muscle composition, serum biochemical indexes, visceral indexes and digestive enzyme activities had been effected with varying degrees of changes. The growth hormone (GH) level in serum was significantly increased in 14D; however, insulin-like growth factor-1 (IGF-1) showed the opposite trend. The neuropeptide Y (npy) mRNA level in brain was significantly improved in 7D; peptide YY (pyy) mRNA level in intestine was significantly decreased during fasting. After refeeding, the final body weight, percentage weight gain, specific growth rate, feed intake, feed efficiency and protein efficiency ratio showed no difference between 0D and 3D. The changes of whole-body and muscle composition, serum biochemical indexes, visceral indexes and digestive enzyme activities had taken place in varying degrees. GH levels in 3D and 7D were significantly higher than those in the 0D; the IGF-1 content decreased significantly during refeeding. There was no significant difference in npy and pyy mRNA levels. These results indicated that short-term fasting followed by refeeding resulted in full compensation and the physiological and biochemical effects on A. dabryanus were the lowest after 3 d of starvation and 14 d of refeeding. Additionally, compensation in A. dabryanus may be mediated by appetite genes and GH, and the degree of compensation is also affected by the duration of starvation.

Highly transparent and conductive p-type CuI films by optimized solid-iodination at room temperature.

p-type CuI films with optimized optoelectronic performance were synthesized by solid-phase iodination of Cu3N precursor films at room temperature. The effects of the deposition power of Cu3N precursors on the structural, electrical, and optical properties of the CuI films were systematically investigated. X-ray diffraction results show that all the CuI films possess a zinc-blende structure. When the deposition power of Cu3N precursors was 140 W, the CuI films present a high transmittance above 84% in the visible region, due to their smaller root-mean-square roughness values of 9.23 nm. Moreover, these films also have a low resistivity of 1.63 × 10-2Ω·cm and a boosted figure of merit of 140.7 MΩ-1. These results are significant achievements among various p-types TCOs, confirming the promising prospects of CuI as a p-type transparent semiconductor applied in transparent electronics.

High-Fidelity NIR-II Multiplexed Lifetime Bioimaging with Bright Double Interfaced Lanthanide Nanoparticles.

Fluorescence lifetime imaging provides more possibility of in vivo multiplexing in second near infrared (NIR-II) window. However, it still faces the obstacle that fluorescent probes with differentiable lifetime often exhibit quite different fluorescence intensity, especially the short lifetime usually accompanies with a weak fluorescence intensity, resulting in the difficulty for simultaneously decoding multiplexed lifetime information due to the interference of background noise. To facilitate high-fidelity lifetime multiplexed imaging, we developed a series of Er3+ doped double interface fluorescent nanoprobes (Er-DINPs): α-NaYF4 @NaErF4 : Ce@NaYbF4 @NaErF4 : Ce@NaYF4 with strong fluorescence intensity and easily distinguishable fluorescence lifetime. Both in vitro and in vivo experimental results confirmed the advantage of these probes with comparable fluorescence intensity for high-fidelity multiplexed lifetime bioimaging.

Fluorinated Gadolinium Chelate-Grafted Nanoconjugates for Contrast-Enhanced T1-Weighted 1H and pH-Activatable 19F Dual-Modal MRI.

Magnetic resonance imaging (MRI) is one of the most popular imaging techniques, which offers an ionization-free noninvasive means for imaging deep tissues with high resolution. Conventional 1H MRI is well versed in providing detailed anatomical information but suffers from low contrast for tracking biomarkers because of the abundance of water in living bodies. 19F MRI with negligible endogenous background interference enables highly sensitive detection of biomolecular targets and has drawn extensive attention from the biomedical research community recently. However, this imaging technique only acquires the "hot spot" signals of exogenous 19F nucleus-containing imaging probes. 1H/19F MRI dual-modal imaging is expected to compensate for the limitations of either single-modal imaging and accomplish synergistic morphological and physiological imaging. Herein, we report a highly biocompatible nanoconjugate composed of pH-responsive 19F nucleus-bearing Gd3+ chelates, which enables significant contrast enhancement for T1-weighted 1H MRI and permits pH-responsive activation of 19F signals for 19F MRI, providing both clear anatomical details of living bodies and the biorelevant molecular information with low background interference. This nanoconjugate facilitates sensitive and accurate detection of tumors with contrast-enhanced T1-weighted 1H and pH-activatable 19F dual-modal imaging on a single MRI scanner.

[The Effects and Mechanisms of Dihydroartemisinin on Influenza A Virus H1N1 Induces TNF-α and IL-6 Expression in Bronchial Epithelial Cells].

OBJECTIVE: To investigate the effects of dihydroartemis (DHA) on influenza A virus (IAV) A/PR/8/34 (H1N1) induces the pro-inflammatory factor and protein of extracellular signal regulated kinase (ERK) signaling pathway expression in bronchial epithelial cells. METHODS: The BEAS-2B cells were treated with different concentrations of DHA (i.e.,0， 12.5, 25，50 and 100 µmol/L) for 24 h and the effect of DHA on the viability of BEAS-2B cells were measure by CCK8 method. The BEAS-2B cells were absorbed with IAV for 1 h, and then were treated with different concentrations of DHA (i.e., 12.5, 25 and 50 µmol/L) for 24 h, meanwhile, the normal control group and IAV group were established. The mRNA and protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6) were measured by real time quantitative PCR (RT-qPCR) and enzyme linked immunosorbent assay (ELISA), the expression levels of phospho-ERK (p-ERK) proteins were tested by Western blot (WB). Then, an ERK agonist (20 ng/mL) was used to treat BEAS-2B cells (the groups were divided into normal control group, DHA group, DHA+IAV group, ERK agonist group and DHA+IAV+ERK agonist group) for 24 h, and to observe the effect of DHA on inhibiting IAV induce the TNF-α, IL-6 and p-ERK expression in the BEAS-2B cells. RESULTS: The BEAS-2B cells viability was not significantly different from that of the normal control group after treatment with DHA (i.e., 12.5, 25, and 50 µmol/L). The expression levels of TNF-α, IL-6 mRNA and TNF-α, IL-6, p-ERK protein in IAV group were significantly up-regulated compared with that in the normal control group ( P<0.05), meanwhile, compared with the IAV group, the expression levels of TNF-α, IL-6 mRNA and TNF-α, IL-6, p-ERK protein showed dose-dependent decrease in IAV+DHA group ( P<0.05). However, ERK agonists attenuated the DHA inhibit IAV induced the proinflammatory factors TNF-α, IL-6 secretion and the p-ERK protein expression of ERK signaling pathway in BEAS-2B cells. CONCLUSION: These data suggest that DHA can inhibit IAV induces the TNF-α and IL-6 expression in BEAS-2B cells through ERK signaling pathway.