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The high level of reactive oxygen species (ROS) in the rheumatoid arthritis (RA) microenvironment (RAM) and its persistent inflammatory nature can promote damage to joints, bones, and the synovium. Targeting strategies that integrate effective RAM regulation with imaging-based monitoring could lead to improvements in the diagnosis and treatment of RA. Here, we report the combined use of small interfering RNAs (siRNAs T/I ) and Prussian blue nanoparticles (PBNPs) to silence the expression of proinflammatory cytokines TNF-α/IL-6 and scavenge the ROS associated with RAM. To enhance the in vitro and in vivo biological stability, biocompatibility, and targeting capability of the siRNAs T/I and PBNPs, macrophage membrane vesicles were used to prepare biomimetic nanoparticles, M@P-siRNAs T/I . The resulting constructs were found to suppress tumor necrosis factor-α/interleukin-6 expression and overcome the hypoxic nature of RAM, thus alleviating RA-induced joint damage in a mouse model. The M@P-siRNAs T/I of this study could be monitored via near-infrared photoacoustic (PA) imaging. Moreover, multispectral PA imaging without the need for labeling permitted the real-time evaluation of M@P-siRNAs T/I as a putative RA treatment. Clinical microcomputed tomography and histological analysis confirmed the effectiveness of the treatment. We thus suggest that macrophage-biomimetic M@P-siRNAs T/I and their analogs assisted by PA imaging could provide a new strategy for RA diagnosis, treatment, and monitoring.

Background Endometriosis (EMT) is one of the common diseases of women of childbearing age. EMT destroys the anatomical structure of the pelvis, which leads to abnormal ovulation and endocrine abnormalities. It also affects embryo implantation and makes patients infertile. Recently, it is confirmed that Chinese medicine also have an excellent clinical efficacy on EMT. Compared with the conventional western medicine treatment, it effectively relieve pain and other concomitant symptoms. Methods and analysis The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and CNKI. Major results the overall effective rate, VAS score. Secondary outcomes blood serum estradiol (E2), progesterone (P), Follicle-Stimulating Hormone (FSH), adverse events. Data will be collected independently by 2 researchers, and the risk of bias in meta-analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions". All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. Results The curative effect and safety of Chinese herbal compound prescription treatment for EMT patients will be evaluated systematically. Conclusion The systematic review of this study will summarize the currently published evidence of Chinese herbal compound prescription treatment for EMT to further guide its promotion and application. Ethics and dissemination The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OPEN SCIENCE FRAMEWORK (OSF) REGISTRATION NUMBER:: https://osf.io/p5nrk.

Photoacoustic imaging (PAI) relies on the use of contrast agents with high molar absorptivity in the NIR-I/NIR-II region. Expanded porphyrins, synthetic analogues of natural tetrapyrrolic pigments (e.g. heme and chlorophyll), constitute as potentially attractive platforms due to their NIR-II absorptivity and their ability to respond to stimuli. Here, we evaluate two expanded porphyrins, naphthorosarin (1) and octaphyrin (4), as stimuli responsive PA contrast agents for functional PAI. Both undergo proton-coupled electron transfer to produce species that absorb well in the NIR-II region. Octaphyrin (4) was successfully encapsulated into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG2000) nanoparticles to afford OctaNPs. In combination with PAI, OctaNPs allowed changes in the acidic environment of the stomach to be visualized and cancerous versus healthy tissues to be discriminated., In this study, two expanded porphyrins, octaphyrin and naphthorosarin were evaluated as potential PA agents. The nanoparticle encapsulation of octaphyrin successfully enabled the visualization of acidic environments and the discrimination between cancerous and healthy tissues.

Rheumatoid arthritis (RA) is the most common type of autoimmune arthritis. Hypoxia-inducible factor-1α (HIF-1α) as a transcription factor in response to hypoxia suggests that it could be a potential therapeutic target for the treatment of RA. In this study, we assessed whether the HIF pathway blockade attenuates the manifestations of RA in the collagen-induced arthritis (CIA) rat model. We constructed a short hairpin RNA (shRNA) lentiviral expression vector targeting HIF-1α (pLVX-shRNA-HIF-1α) and to achieve HIF-1α RNA interference. Quantitative RT-PCR, immunofluorescence staining, and western blot were used to detect the expressions of HIF-1α, vascular endothelial growth factor (VEGF), phsopho (p)-p65, and p-IКBɑ mRNA and protein, respectively. Micro-computed tomography was used to investigate joint morphology at different time points after CIA induction. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to monitor the expression of inflammatory cytokines. In vitro analyses revealed that pLVX-shRNA-HIF-1α effectively inhibited the expression of HIF-1α and VEGF and led to the activation of p-65 and p-IКBɑ, as well as decreased proinflammatory cytokine expression in cell culture. Inhibition of HIF-1α in rats decreased signs of a systemic inflammatory condition, together with decreased pathological changes of RA. Moreover, downregulation of HIF-1α expression markedly reduced the synovitis and angiogenesis. In conclusion, we have shown that pharmacological inhibition of HIF-1 may improve the clinical manifestations of RA. Keywords: lentivirus, rheumatoid arthritis, HIF-1α, shRNA

Objectives: The objective of this study was to demonstrate the feasibility of using noninvasive photoacoustic imaging technology along with novel semiconducting polymer nanoparticles for in vivo identifying inflammatory components in carotid atherosclerosis and assessing the severity of inflammation using mouse models. Methods and Results: Healthy carotid arteries and atherosclerotic carotid arteries were imaged in vivo by the noninvasive photoacoustic imaging system. Molecular probes PBD-CD36 were used to label the inflammatory cells to show the inflammation information by photoacoustic imaging. In in vivo imaging experiments, we observed the maximum photoacoustic signal enhancement of 4.3, 5.2, 8 and 16.3 times between 24 h post probe injection and that before probe injection in four carotid arteries belonging to three atherosclerotic mice models. In the corresponding carotid arteries stained with CD36, the ratio of 0.043, 0.061, 0.082 and 0.113 was found between CD36 positive (CD36(+)) expression area and intima-media area (P < 0.05). For the CD36(+) expression less than 0.008 in eight arteries, no photoacoustic signal enhancement was found due to the limited system sensitivity. The photoacoustic signal reflects CD36(+) expression in plaques, which shows the feasibility of using photoacoustic imaging for in vivo assessment of carotid atherosclerosis. Conclusion: This research demonstrates a semiconducting polymer nanoparticle along with photoacoustic technology for noninvasive imaging and assessment of inflammation of carotid atherosclerotic plaques in vivo.

Rationale: Insufficient penetration and accumulation of theranostic payloads in solid tumors greatly challenge the clinical translation of cancer nanomedicines. To address this challenge, we synthesized natural melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets with good biocompatibility and self-assembling ability. Methods: We used an opto-acoustic synergistic irradiation (OASI) method that was effective at lower energy levels than ultrasound- or laser-only irradiation to safely vaporize the nanodroplets and to cavitate the generated microbubbles for mechanically enhancing intratumoral delivery. The delivered melanin and doxorubicin inside the tumors mediated secondary chemo-photothermal therapy under laser irradiation to fully kill cancer cells. Results: In vivo animal experiments demonstrated direct mechanical disruption of tumor structures (H&E staining), enhanced intratumoral penetration of melanin (photoacoustic imaging), and efficient intratumoral accumulation of doxorubicin (fluorescent imaging). Anti-tumor experiments demonstrated that the nanodroplets combined with OASI treatment and subsequent laser irradiation could efficiently eliminate melanoma tumors. Conclusion: Melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets hold great promise for translational sono-chemo-photothermal cancer therapy.

Significance Photoacoustic (PA) imaging can provide information about deep-seated biological tissues. Unfortunately, signal intensity and resolution can be limited by background signals arising from endogenous chromophores. Photochromism, the use of agents that go from colorless to colored, has been suggested to be a promising avenue to overcome this limitation. However, a viable method that allows practical applications of this so-called background-suppressed PA imaging is still lacking. Here, we report the engineering of a phytochrome-based reporter protein (m Dr BphP-PCMm/F469W) that displays high photoswitching contrast. Its expression in Escherichia coli enables point-specific imaging within the tumor region over several days and permits PA monitoring of deep-seated tumor tissues via reduction of background signals.

Carbon dots that exhibit near-infrared fluorescence (NIR CDs) are considered emerging nanomaterials for advanced biomedical applications with low toxicity and superior photostability and targeting compared to currently used photoluminescence agents. Despite progress in the synthesis of NIR CDs, there remains a key obstacle to using them as an in vivo theranostic agent. This work demonstrates that the newly developed sulfur and nitrogen codoped NIR CDs are highly efficient in photothermal therapy (PTT) in mouse models (conversion efficiency of 59%) and can be readily visualized by photoluminescence and photoacoustic imaging. The real theranostic potential of NIR CDs is enhanced by their unique biodistribution and targeting. Contrary to all other nanomaterials that have been tested in biomedicine, they are excreted through the body’s renal filtration system. Moreover, after intravenous injection, NIR CDs are accumulated in tumor tissue via passive targeting, without any active species such as antibodies. Due to their accumulation in tumor tissue without the need for intratumor injection, high photothermal conversion, excellent optical and photoacoustic imaging performance, and renal excretion, the developed CDs are suitable for transfer to clinical biomedical practice., Carbon dots: Lighting up for cancer therapy and diagnosis ‘Carbon dot’ nanoparticles composed largely of carbon, but doped with sulfur and nitrogen, accumulate within cancer cells and absorb near-infrared laser light to generate cell-killing heat. The procedure was developed and tested by researchers in China and the Czech Republic, led by Songnan Qu at the Changchung Institute of Optics, Fine Mechanics and Physics. The nanoparticles accumulated passively in tumors after intravenous injection into mice, with no specific targeting methods required. Tumors were effectively eradicated by the highly efficient conversion of the light energy into heat. The nanoparticles are biocompatible and are eventually excreted harmlessly in urine. In addition to the potential for treating cancer, diagnosis can also be assisted using the particles’ fluorescent properties. This combination of therapy and diagnosis – ‘theranostics’ – can now be further developed and explored for use in patients.

The present work indicated the green synthesis, characterization, cytotoxicity, antioxidant, and anti-human ovarian cancer activities of gold nanoparticles containing Curcumae Kwangsiensis Folium (Leaf) aqueous extract. Characterization of gold nanoparticles was done by Field Emission Scanning Electron Microscopy (FE‐SEM), Transmission Electron Microscopy (TEM), Fourier Transformed Infrared Spectroscopy (FT‐IR), and UV–Visible Spectroscopy (UV-Vis). MTT assay was used on common ovarian cancer cell lines i.e., SW-626, PA-1, and SK-OV-3 to survey the cytotoxicity and anti-ovarian cancer effects of gold chloride, Curcumae Kwangsiensis Folium leaf aqueous extract, and gold nanoparticles. The best results of cytotoxicity and anti-ovarian cancer properties were seen in the case of gold nanoparticles. They had very low cell viability and high anti-ovarian cancer activities dose-dependently against PA-1, SW-626, and SK-OV-3 cell lines without any cytotoxicity on the normal cell line (HUVEC). For investigating the antioxidant properties of gold chloride, Curcumae Kwangsiensis Folium leaf aqueous extract, and gold nanoparticles, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. The best results of antioxidant properties were seen in the case of gold nanoparticles. They inhibited half of the DPPH molecules in the concentration of 153 µg/mL. Maybe significant anti-human ovarian cancer potentials of gold nanoparticles synthesized by Curcumae Kwangsiensis Folium leaf aqueous extract against common human ovarian cancer cell lines are linked to their antioxidant activities.

Objective To investigate the molecular mechanism of hypoxia-induced rheumatoid arthritis synovial fibroblast (RASF) activation via Notch-1 and Notch-3 signaling, and to evaluate its potential as a therapeutic target. Methods Expression of Notch-1 intracellular domain (N1ICD), N3ICD, and hypoxia-inducible factor 1α (HIF-1α) was assessed by immunhistology in synovial tissue from patients with RA. RASFs were cultured under hypoxic conditions and normoxic conditions with or without small interfering RNAs (siRNAs), and N1ICD and N3ICD were overexpressed under normoxic conditions. Rats with collagen-induced arthritis (CIA) were administered LY411575 (inhibitor of N1ICD and N3ICD) for 15 days and 28 days, and its therapeutic efficacy was assessed by histologic and radiologic evaluation of the rat synovial tissue, and by analysis of inflammatory cytokine production in the serum of rats. Results N1ICD, N3ICD, and HIF-1α were expressed abundantly in the synovial tissue of RA patients. HIF-1α was shown to directly regulate the expression of Notch-1 and Notch-3 genes under hypoxic conditions. Moreover, hypoxia-induced N1ICD and N3ICD expression in RASFs was blocked by HIF-1α siRNA. Notch-1 siRNA and Notch-3 siRNA inhibited hypoxia-induced RASF invasion and angiogenesis in vitro, whereas overexpression of N1ICD and N3ICD promoted these processes. In addition, Notch-1 was shown to regulate RASF migration and epithelial-mesenchymal transition under hypoxic conditions, whereas Notch-3 was shown to regulate the processes of anti-apoptosis and autophagy. Furthermore, in vivo studies in rats with CIA showed that the N1ICD and N3ICD inhibitor LY411575 had a therapeutic effect in terms of ameliorating the symptoms and severity of the disease. Conclusion This study identified a functional link between HIF-1α, Notch-1, and Notch-3 signaling in regulating activation of RASFs and the processes involved in the pathogenesis of RA.

The NIR absorptivity of the metallotexaphyrin derivatives MMn, MGd, and MLu for photoacoustic (PA)-based imaging is explored in this study. All three complexes demonstrated excellent photostabilities; however, MMn provided the greatest PA signal intensities in both doubly distilled water and RAW 264.7 cells. In vivo experiments using a prostate tumor mouse model were performed. MMn displayed no adverse toxicity to major organs as inferred from hematoxylin and eosin (H&E) staining and cell blood count testing. MMn also allowed for PA-based imaging of tumors with excellent in vivo stability to provide 3D tumor diagnostic information. Based on the present findings and previous magnetic resonance imaging (MRI) studies, we believe MMn may have a role to play either as a stand-alone PA contrast agent or as a single molecule dual modal (PA and MR) imaging agent for tumor diagnosis.

Pain Syndrome is a kind of unpleasant subjective feeling caused by poor Qi and blood circulation for many factors inside and outside the body or physical examination found abnormal signs, which is widely scattered in clinical departments. In recent years, Zhuangyi has made much progress in the treatment of gynecological pain diseases, and its curative effect has unique advantages, especially for gynecological diseases such as dysmenorrhea, pelvic inflammatory disease and mammary gland hyperplasia, for the treatment of gynecological diseases of pain, bruising has a significant effect. The characteristic therapy of Zhuangyi has various kinds with obvious characteristics, safe operation, remarkable effect and wide application prospect.

Objective: To investigate the expression of TNF-a and NF-kB in the uterus of chronic pelvic inflammatory disease (CPID) model rats. Methods: 40 female rats that adaptive fed for 5 days were randomly divided into normal group, model group, high dose group, medium dose group and low dose group. In addition to the normal group, the rats in each group were made chronic pelvic inflammatory model by mechanical injury combined with implantation of bacteria. The rats in each group were administrated by gavage for 20 days. After the last administration, the level of TNF-a and NF-kB in serum was measured by ELASA method. Results: (1) after the establishment of the model, the uterus of the chronic pelvic inflammatory model rats showed the pathological damage of chronic inflammation; the levels of TNF-a and NF-kB in serum were higher than those in the normal group, the difference was statistically significant (P

The March 3 Song Fair of Zhuang nationality is not only an important place and form for spreading Zhuang culture, but also contains rich health care ideas. This article briefly discusses the meaning and value of March 3 in Zhuang people based on health preservation.

Perimenopause syndrome refers to the syndrome of the disorders of multiple systems of women around menopause caused by the reduction in secreted estrogen and is also known as menopause syndrome. Its pathogenesis involves increasing age, the abatement of ovarian function, and psychological change caused by the increasing life pressure. The above factors lead to physical and mental changes in postmenopausal women. This paper summarizes the pathogenesis of perimenopause from the perspective of gene studies and existing experimental studies and provide some ideas for clinical treatment and research.

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS2–ICG hybrid with indocyanine green (ICG) conjugated to the surface of MoS2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine.

Photoacoustic imaging (PAI) has emerged as a promising clinical technology, thanks to its high-resolution in deep tissues. However, the lack of specificity towards analytes limits further application of the PA probe in molecular imaging. To this end, we herein report a PA and fluorescence (FL) dual-modal probe for the selective detection of ascorbic acid (AA). To realize this design, cobalt oxyhydroxide (CoOOH) was adopted as a multifunctional platform (PA contrast agent, FL quencher and specific oxidant to AA) and hybridized with red-emissive carbon dots (RCDs). In the presence of AA, CoOOH is reduced to Co2+ and meanwhile releases RCDs, resulting in the decrease of PA and recovery of FL signals. We demonstrated the AA detection capabilities of the probe in complicated biological fluids (human serum and urine), living cells, and dual-modal FL/PA imaging in vivo. This work revealed the PAI capacity of CoOOH for the first time, which may inspire researchers to design other CoOOH-based PA probes and further employ RCDs in biology and the clinic.

Phototheranostic technology based on photoacoustic imaging (PAI) and photothermal therapy (PTT) is emerging as a powerful tool for tumor theranostic applications. For effective tumor eradication, a novel PAI/PTT theranostic nanoagent with an excellent optical absorption and photothermal capability is highly desired. Herein, we present a new PAI/PTT nanohybrid named sMoSe2-ICG NSs by covalently conjugating aminated indocyanine green (ICG) onto a single layer of molybdenum selenide nanosheets (sMoSe2 NSs). We first validate the sMoSe2-ICG NS agent for the PAI and PTT effect in vitro and then use it for highly-sensitive PAI guided highly efficient tumor PTT in vivo. The sMoSe2-ICG NS hybrid possesses several advantages for PAI/PTT applications: (1) the sMoSe2-ICG NSs have strong absorbance in the broad near-infrared (NIR) region, enabling a highly efficient PAI/PTT theranostic effect and the selection of the most widely used excitation wavelength of 808 nm for PTT; (2) the photothermal ability of ICG in sMoSe2-ICG NSs is augmented due to ICG aggregation induced fluorescence quenching and the re-absorbance of ICG fluorescence by sMoSe2 NSs, which further enhances the PAI/PTT theranostic effect. (3) The characteristic absorption peak of sMoSe2-ICG NSs is red-shifted compared to free ICG, resulting in a higher PAI signal-to-noise ratio (SNR) in vivo. Thus, combined with the good stability, high biocompatibility and minimal toxicity properties, the obtained sMoSe2-ICG NSs hybrid has bright prospects for use in future PAI/PTT clinical applications.

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and is the second leading cause of mortality in cancer patients. Thus, accurate diagnosis and effective treatment of the malignancy is very critical for HCC patients. The photoacoustic (PA) nanoparticle with ultra-sensitive imaging signals and high photothermal conversion efficacy is a new and promising method for achieving the desired goals. In this study, we have synthesized a novel lipid nanoparticle based on IR-1061 dyes by encapsulating the dye into a liposome which was modified by DSPE-PEG2000. We conducted serial experiments to investigate the PA diagnosis performance, the surgical navigation, and the photothermal therapy (PTT) capability of the novel nanoparticle (Polipo-IR NP) in nude mice bearing HCC. The results showed that our novel nanoparticles exhibited strong laser energy absorption at 1064 nm wavelength, high photothermal conversion efficacy (45.25%) and ultra-sensitive PA signals. The in vivo PA studies demonstrated that the proposed nanoparticles could diagnose tumors non-invasively and accurately with a strong signal-to-noise ratio of 5.98 ± 0.23 at 3 h post-injection and could successfully achieve radical resection of tumors intraoperatively. Furthermore, the PTT test demonstrated a remarkable cancer cell killing ability because of its high photothermal conversion efficacy. The excellent photostability and high biocompatibility were also validated by in vitro and in vivo experiments. Thus, our proposed NIR-II PA and PTT nanoparticles based on the IR-1061 dye would potentially provide novel insights into understanding polymethine dyes in nanomedicine and would greatly benefit early diagnosis and treatment of HCC patients.

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window (especially at 1064 nm) has the benefits of low background signal, high spatial resolution and deep tissue penetration. Here we report a semiconducting polymer nanoparticle (PDPPTBZ NP) and demonstrate its potential as a contrast agent for PA imaging of orthotopic brain tumors, using a 1064 nm pulsed laser as a light source. PDPPTBZ NPs have maximum absorption at 1064 nm with a mass extinction coefficient of 43 mL mg−1 cm−1, which is the highest value reported so far in this region. The high photothermal conversion efficiency (67%) and near non-fluorescence impart PDPPTBZ NPs with excellent PA properties. We used PDPPTBZ NP-containing agar gel phantoms even at a low concentration (50 μg mL−1) to successfully image to a depth of 4 cm (of chicken-breast tissue), with an ultralow power fluence (4 mJ cm−2). Furthermore, we could clearly visualize a glioma tumor in a mouse at a depth of 3.8 mm below the skull. This study demonstrates that PDPPTBZ NPs display great potential as a NIR-II PA contrast agent for high quality deep tissue imaging.

Photomediated cancer therapy, mainly including photothermal (PT) therapy (PTT) and photodynamic therapy (PDT), has attracted tremendous attention in recent years thanks to its noninvasive and stimuli-responsive features. The single mode of PTT or PDT, however, has obvious drawbacks, either requiring high-power laser irradiation to generate enough heat or only providing limited efficacy due to the hypoxia nature inside tumors. In addition, the reported synergistic PTT/PDT generally utilized two excitation sources to separately activate PTT and PDT, and the problem of high-power laser irradiation for PTT was still not well solved. Herein, a new concept, loading a small amount of photosensitizers onto a PTT agent (both of them can be triggered by a single-near-infrared (NIR) laser), was proposed to evade the shortcomings of PTT and PDT. To validate this idea, minute quantities of photosensitizer chlorin e6 (Ce6) (0.56% of mass) were anchored onto amino-rich red emissive carbon dots (RCDs) that possess superior photothermal (PT) character under 671 nm NIR laser (PT conversion efficiency to be 46%), and meanwhile the PDT of Ce6 can be activated by this laser irradiation as well. The findings demonstrate that Ce6-modified RCDs (named Ce6-RCDs) offer much higher cancer therapy efficacy under a reduced laser power density (i.e., 0.50 W cm-2 at 671 nm) in vitro and in vivo than the equivalent RCDs or Ce6 under the same irradiation conditions. Besides, the Ce6-RCDs also exhibit multimodal imaging capabilities (i.e., fluorescence (FL), photoacoustic (PA), and PT), which can be employed for guidance of the phototherapy process. This study suggests not only a strategy to enhance cancer phototherapy efficacy but also a promising candidate (i.e., Ce6-RCDs) for multimodal FL/PA/PT imaging-guided and single-NIR-laser-triggered synergistic PTT/PDT for cancers by a reduced irradiation power.

Multi-modality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging, for both the diagnosis and therapy of cancer.

Exogenous contrast-agent-assisted NIR-II optical-resolution photoacoustic microscopy imaging (ORPAMI) holds promise to decipher wide-field 3D biological structures with deep penetration, large signal-to-background ratio (SBR), and high maximum imaging depth to depth resolution ratio. Herein, NIR-II conjugated polymer nanoparticle (CP NP) assisted ORPAMI is reported for pinpointing cerebral and tumor vasculatures. The CP NPs exhibit a large extinction coefficient of 48.1 L g-1 at the absorption maximum of 1161 nm, with an ultrahigh PA sensitivity up to 2 µg mL-1 . 3D ORPAMI of wide-field mice ear allows clear visualization of regular vasculatures with a resolution of 19.2 µm and an SBR of 29.3 dB at the maximal imaging depth of 539 µm. The margin of ear tumor composed of torsional dense vessels among surrounding normal regular vessels can be clearly delineated via 3D angiography. In addition, 3D whole-cortex cerebral vasculatures with large imaging area (48 mm2 ), good resolution (25.4 µm), and high SBR (22.3 dB) at a depth up to 1001 µm are clearly resolved through the intact skull. These results are superior to the recently reported 3D NIR-II fluorescence confocal vascular imaging, which opens up new opportunities for NIR-II CP-NP-assisted ORPAMI in various biomedical applications.

Photoacoustic (PA) imaging, as a fast growing technology that combines the high contrast of light and large penetration depth of ultrasound, has demonstrated great potential for molecular imaging of cancer. However, PA molecular imaging of orthotopic brain tumors is still challenging, partially due to the limited options and insufficient sensitivity of available PA molecular probes. Here, the direct formation of single-layer (S-MoS2), few-layer (F-MoS2), and multi-layer (M-MoS2) nanosheets by the albumin-assisted exfoliation without further surface modifications is reported. It is demonstrated that the PA effect of the MoS2 nanosheets is highly dependent on their layered nanostructures. Decreasing the number of nanosheet layers from M-MoS2 to S-MoS2 can both significantly enhance the near-infrared light absorption and improve the elastic properties of the nanomaterial, resulting in greatly amplified PA effect. The in vitro experiments demonstrate that the prepared S-MoS2 with excellent biocompatibility can be efficiently internalized into U87 glioma cells, producing strong PA signals for highly sensitive detection of brain tumor cells, with a detection limit of ≈100 cells. Intravenous administration of S-MoS2 to both U87 subcutaneous and orthotopic tumor-bearing mice shows highly efficient tumor retention and significantly enhanced PA contrast. Tumor tissue ≈1.5 mm below the skull can still be clearly visualized in vivo. Previous studies suggest that the fabricated S-MoS2 with amplified PA effect have high potential to serve as an efficient nanoplatform for sensitive PA molecular imaging and hold promising prospect for translational medicine.

Photoacoustic (PA) imaging is a rapidly emerging biomedical imaging modality that is capable of visualizing cellular and molecular functions with high detection sensitivity and spatial resolution in deep tissue. Great efforts and progress have been made on the development of various PA imaging technologies with improved resolution and sensitivity over the past two decades. Various PA probes with high contrast have also been extensively developed, with many important biomedical applications. In comparison with chemical dyes and nanoparticles, genetically encoded probes offer easier labeling of defined cells within tissues or proteins of interest within a cell, have higher stability in vivo, and eliminate the need for delivery of exogenous substances. Genetically encoded probes have thus attracted increasing attention from researchers in engineering and biomedicine. In this review, we aim to provide an overview of the existing PA imaging technologies and genetically encoded PA probes, and describe further improvements in PA imaging techniques and the near-infrared photochromic protein BphP1, the most sensitive genetically encoded probe thus far, as well as the potential biomedical applications of BphP1-based PA imaging in vivo.

The progressive debilitating nature of rheumatoid arthritis (RA) combined with its unknown etiology and initial similarity to other inflammatory diseases makes early diagnosis a significant challenge. Early recognition and treatment of RA is essential for achieving effective therapeutic outcome. NIR-II photoacoustic (PA) molecular imaging (PMI) is emerging as a promising new strategy for effective diagnosis and treatment guidance of RA, owing to its high sensitivity and specificity at large penetration depth. Herein, an antirheumatic targeted drug tocilizumab (TCZ) is conjugated to polymer nanoparticles (PNPs) to develop the first NIR-II theranostic nanoplatform, named TCZ-PNPs, for PA-imaging-guided therapy of RA. The TCZ-PNPs are demonstrated to have strong NIR-II extinction coefficient, high photostability and excellent biocompatibility. NIR-II PMI results reveal the excellent targeting abilities of TCZ-PNPs for the effective noninvasive diagnosis of RA joint tissue with a high signal-to noise ratio (SNR) of 35.8 dB in 3D PA tomography images. Remarkably, one-month treatment and PA monitoring using TCZ-PNPs shows RA is significantly suppressed. In addition, the therapeutic evaluation of RA mice by NIR-II PMI is shown to be consistent with clinical micro-CT and histological analysis. The TCZ-PNPs-assisted NIR-II PMI provides a new strategy for RA theranostics, therapeutic monitoring and the beyond.

Although photoacoustic imaging combined with second near infrared (NIR II) molecular probes for tumor diagnosis has drawn tremendous attention during the past few decades, the targeted photoacoustic imaging of orthotopic hepatocellular carcinoma (HCC) still remains a challenge due to high liver vascularization and non-specificity of probes in liver tumors. Herein, we report on cyclic arginine-glycine-aspartic acid (cRGD) peptide conjugated ultrasmall CuS nanoparticles (CuS@BSA-RGD NPs) which encapsulate bovine serum albumin (BSA) and possess high optical absorption at 1064 nm. The encapsulation of BSA results in great biocompatibility of CuS@BSA-RGD NPs along with excellent photostability and physiological stability. The cRGD conjugation enables the improvement of tumor uptake of CuS@BSA-RGD NPs by virtue of its positive tumor cell targeting capability. The efficient accumulation of CuS@BSA-RGD NPs in the tumor over time after intravenous administration to orthotopic HCC bearing mice was achieved, which resulted in highly sensitive photoacoustic visualization of the tumor region. Toxicity studies indicate that CuS@BSA-RGD NPs exhibited negligible systemic toxicity in vivo. The results demonstrate that the CuS@BSA-RGD NPs might hold great promise for future imaging and diagnosis of cancer.

Carbon nanodots (CNDs) with high photothermal conversion efficiency are considered as emerging nanomaterials for advanced biomedical applications attributing to their high biocompatibility, low-cost, and unique photophysical properties. In previous work, supra-CNDs are synthesized exhibiting high absorption in the near-infrared (NIR) region and good NIR photothermal conversion performance. In this work, supra-CNDs are explored as a photothermal agent for photothermal therapy (PTT) and a contrast agent for photoacoustic (PA) imaging, respectively. As a result, in vivo tumor PTT is realized under 655 nm laser irradiation via intratumor injecting supra-CNDs. In vivo PA imaging reveals that supra-CNDs can accumulate in the tumor tissue via the blood circulation after intravenous injection. Moreover, in vivo PTT is conducted after intravenous injection and subsequent tumor accumulation of supra-CNDs, and the lives of mice are prolonged due to the tumor growth inhibition after PTT. These attractive properties indicate that the supra-CNDs can be used as biomedical agents for PA imaging and tumor therapy.

Phototheranostic technology based on photoacoustic imaging (PAI) and photothermal therapy (PTT) is emerging as a powerful tool for tumor theranostic applications. For effective tumor eradication, a novel PAI/PTT theranostic nanoagent with an excellent optical absorption and photothermal capability is highly desired. Herein, we present a new PAI/PTT nanohybrid named sMoSe2-ICG NSs by covalently conjugating aminated indocyanine green (ICG) onto a single layer of molybdenum selenide nanosheets (sMoSe2 NSs). We first validate the sMoSe2-ICG NS agent for the PAI and PTT effect in vitro and then use it for highly-sensitive PAI guided highly efficient tumor PTT in vivo. The sMoSe2-ICG NS hybrid possesses several advantages for PAI/PTT applications: (1) the sMoSe2-ICG NSs have strong absorbance in the broad near-infrared (NIR) region, enabling a highly efficient PAI/PTT theranostic effect and the selection of the most widely used excitation wavelength of 808 nm for PTT; (2) the photothermal ability of ICG in sMoSe2-ICG NSs is augmented due to ICG aggregation induced fluorescence quenching and the re-absorbance of ICG fluorescence by sMoSe2 NSs, which further enhances the PAI/PTT theranostic effect. (3) The characteristic absorption peak of sMoSe2-ICG NSs is red-shifted compared to free ICG, resulting in a higher PAI signal-to-noise ratio (SNR) in vivo. Thus, combined with the good stability, high biocompatibility and minimal toxicity properties, the obtained sMoSe2-ICG NSs hybrid has bright prospects for use in future PAI/PTT clinical applications.

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS2–ICG hybrid with indocyanine green (ICG) conjugated to the surface of MoS2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine. Electronic supplementary material The online version of this article (10.1007/s40820-018-0202-8) contains supplementary material, which is available to authorized users.

The ergodic hypothesis is a basic hypothesis typically invoked in atmospheric surface layer (ASL) experiments. The ergodic theorem of stationary random processes is introduced to analyse and verify the ergodicity of atmospheric turbulence measured using the eddy-covariance technique with two sets of field observational data. The results show that the ergodicity of atmospheric turbulence in atmospheric boundary layer (ABL) is relative not only to the atmospheric stratification but also to the eddy scale of atmospheric turbulence. The eddies of atmospheric turbulence, of which the scale is smaller than the scale of the ABL (i.e. the spatial scale is less than 1000 m and temporal scale is shorter than 10 min), effectively satisfy the ergodic theorems. Under these restrictions, a finite time average can be used as a substitute for the ensemble average of atmospheric turbulence, whereas eddies that are larger than ABL scale dissatisfy the mean ergodic theorem. Consequently, when a finite time average is used to substitute for the ensemble average, the eddy-covariance technique incurs large errors due to the loss of low-frequency information associated with larger eddies. A multi-station observation is compared with a single-station observation, and then the scope that satisfies the ergodic theorem is extended from scales smaller than the ABL, approximately 1000 m to scales greater than about 2000 m. Therefore, substituting the finite time average for the ensemble average of atmospheric turbulence is more faithfully approximate the actual values. Regardless of vertical velocity or temperature, the variance of eddies at different scales follows Monin–Obukhov similarity theory (MOST) better if the ergodic theorem can be satisfied; if not it deviates from MOST. The exploration of ergodicity in atmospheric turbulence is doubtlessly helpful in understanding the issues in atmospheric turbulent observations and provides a theoretical basis for overcoming related difficulties.

Solute–vacancy binding energy is a key quantity in understanding solute diffusion kinetics and phase segregation, and may help choice of alloy compositions for future material design. However, the binding energy of solute with vacancy is notoriously difficult to measure and largely unknown in bcc Fe. With first-principles method, we systemically calculate the binding energies of solute (3 p , 4 p , 5 p and 6 p alloying solutes are included) with vacancy, divacancy and solute in bcc Fe. The binding energy of Si with vacancy in the present work is in good consistent with experimental value available. All the solutes considered are able to form stable solute–vacancy, solute–divacancy complexes, and the binding strength of solute–divacancy is about two times larger than that of solute–vacancy. Most solutes could not form stable solute–solute complexes except S, Se, In and Tl. The factors controlling the binding energies are analyzed at last.

Our recent studies have demonstrated the key roles of reactive oxygen species (ROS)-mediated caspase-8- and Bax-dependent apoptotic pathways in dihydroartemisinin (DHA)-induced apoptosis of A549 cells. This report is designed to investigate the proapoptotic mechanisms of DHA in gemcitabine (Gem)-resistant A549 (A549GR) cells. A549GR cells exhibited lower basal antioxidant capacity, higher level of basal ROS and intracellular Fe(2+) than Gem-sensitive A549 (A549) cells. In contrast to the sluggish ROS generation induced by Gem, DHA induced a rapid ROS generation within 30min. Moreover, Gem induced similar ROS generation in both cell lines, while DHA induced more ROS generation in A549GR cells than in A549 cells. More importantly, after treatment with DHA, A549GR cells showed more potent induction in Bax activation, loss of mitochondrial membrane potential (ΔΨm), caspase activation and apoptosis than A549 cells. Furthermore, NAC pretreatment potently prevented DHA-induced ROS generation and loss of ΔΨm as well as apoptosis, and silencing Bax by shRNA or inhibition of one of caspase-3, -8 and -9 also significantly prevented DHA-induced apoptosis in both cell lines, indicating the key roles of ROS and Bax as well as the caspases. Collectively, DHA presents more potent proapoptotic actions in A549GR cells preferentially over normal A549 cells via ROS-dependent apoptotic pathway, in which Bax and caspases are involved.

As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

Here, we developed one-step green reduction and PEGylation of nanosized graphene oxide (NGO) to obtain NrGO/PEG as a photothermally controllable drug delivery system. NrGO/PEG was synthesized by bathing methoxypolyethylene glycol amine (mPEG-NH2) and NGO at 90 °C for 24 h. The NrGO/PEG kept water stability for at least two months, and had ~14-fold increment in near-infrared (NIR) absorbance and ~2-fold increment in resveratrol (RV) loading over the unreduced NGO/PEG via π-π and hydrophobic interactions. Exposure of 4T1 cells to NrGO/PEG for 2 h showed 53.6% uptake ratio, and localization of NrGO/PEG in lysosomes instead of mitochondria. NIR irradiation (808 nm laser at 0.6 W/cm(2)) for 3 min potently enhanced RV release from NrGO/PEG-RV and the cytotoxicity of NrGO/PEG-RV against 4T1 cells, including decrease of cell viability, loss of mitochondrial membrane potential (ΔΨm) and cell apoptosis. Finally, NIR irradiation dramatically enhanced the efficacy of NrGO/PEG-RV in suppressing tumor growth in animal tumor models, further proving the remarkable synergistic action between photothermal effect of NrGO/PEG and RV loaded on NrGO/PEG.

The ERO code has been used to simulate lithium erosion, transport and re-deposition from liquid lithium limiter experiments in FTU. Two different operational cases from LLL experiments with different plasma parameters and surface temperature are modelled. According to the effective lithium sputtering yields, for both cases the lithium erosion is mainly due to physical sputtering rather than evaporation. Furthermore, the modelled re-deposition fraction of evaporated lithium is much higher than that of sputtered lithium, which is due to the shorter ionisation mean free path of thermal lithium atoms. Therefore, the evaporation erosion effect can be neglected compared to physical sputtering when the surface temperature is below 450 °C. According to the simulations, most of the lithium impurities exist in the form of Li+, and the main plasma contamination by lithium ions is low because most of eroded lithium particles are not transported into the core plasma and stay outside of the LCFS. © 2013 Elsevier B.V. All rights reserved.

Multimodality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging. Specifically, photoacoustic and fluorescence dual-modality imaging is gaining much interest because of their non-invasiveness and the complementary nature of the two modalities in terms of imaging resolution, depth, sensitivity, and speed. Herein, using a green and facile method, we synthesize indocyanine green (ICG) loaded, polyethylene glycol (PEG)ylated, reduced nano-graphene oxide nanocomposite (rNGO-PEG/ICG) as a new type of fluorescence and photoacoustic dual-modality imaging contrast. The nanocomposite is shown to have minimal toxicity and excellent photoacoustic/fluorescence signals both in vitro and in vivo. Compared with free ICG, the nanocomposite is demonstrated to possess greater stability, longer blood circulation time, and superior passive tumor targeting capability. In vivo study shows that the circulation time of rNGO-PEG/ICG in the mouse body can sustain up to 6 h upon intravenous injection; while after 1 day, no obvious accumulation of rNGO-PEG/ICG is found in any major organs except the tumor regions. The demonstrated high fluorescence/photoacoustic dual contrasts, together with its low toxicity and excellent circulation life time, suggest that the synthesized rNGO-PEG/ICG can be a promising candidate for further translational studies on both the early diagnosis and image-guided therapy/surgery of cancer. Electronic supplementary material The online version of this article (doi:10.1186/s11671-016-1288-x) contains supplementary material, which is available to authorized users.

The supplementary characterization results of rNGO-PEG/ICG. (DOCX 2405 kb)

Thick SiC coatings of ∼100 μm on graphite tiles, prepared by chemical vapor infiltration of Si into the tiles and the following reactions between Si and C, are used as plasma facing material (PFM) on HT-7 superconducting tokamak and Experimental Advanced Superconducting Tokamak (EAST). With increase in the heating and driving power in EAST, the present plasma facing component (PFC) of the SiC/C tiles bolted to heat sink will be replaced by W coatings on actively cooled Cu heat sink, prepared by vacuum plasma spraying (VPS) adopting different interlayer. The VPS-W/Cu PFC with built-in cooling channels were prepared and mounted into the HT-7 acting as a movable limiter. Behavior of heat load onto the limiter and the material was studied. The Cu coatings on the Inconel 625 tubes were successfully prepared by high velocity air–fuel (HVAF) thermal spraying, being used as the liquid nitrogen (LN2) shields of the in-vessel cryopump for divertor pumping in EAST.

A one-dimensional fluid model, which calculates the modification of density and temperature along the magnetic field and the parallel electrical field in the presence of local impurity sources, has been implemented into the ERO code. The influence of impurity source strength on the local plasma parameters and resulting changes in impurity transport and deposition has been studied. Dedicated TEXTOR experiments of 13 CH 4 injection through roof-like test limiters are modelled for comparison. Modelling with high injection rates (larger than about 4 × 10 18 s −1 ) results in too localized light emission pattern near to the injection hole, and therefore indicates an underestimation of the reduction of electron temperature in the model. Besides, the preliminary results indicate that possible modification of local plasma conditions cannot significantly reduce the modelled 13 C deposition and therefore cannot explain the measured low 13 C deposition efficiency.