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Immunotherapy has dramatically impacted cancer therapy, but it has been challenging to apply immunotherapy to estrogen receptor (ER) positive breast cancer and many other solid tumors that do not display neoantigens. One way to target these tumors is to induce necrosis, which robustly activates immune cells, inducing immunogenic cell death. However, anticancer therapy-induced necrosis was primarily characterized by morphological changes, and the molecular drivers of necrosis were largely obscure. To probe necrosis, we used our necrosis inducing anticancer agents, the small molecules BHPI and second-generation ErSO, which kill cancer cells by hyperactivating the anticipatory unfolded protein response (a-UPR). In orthotopic mouse xenografts, ErSO induces complete regression without recurrence of large, therapy-resistant primary ER positive breast tumors, of most lung, bone, and liver metastases, near complete regression of challenging breast cancer brain metastases and robust responses in PDX and patient derived organoids (PDOs) models. ErSO also induces complete or near complete regression in mouse xenograft models of ER positive ovarian and endometrial cancer. Using genome wide CRISPR-Cas9 screens with negative selection against our necrosis-inducing a-UPR hyperactivators, BHPI and ErSO, we identified the calcium-activated, ATP-inhibited, plasma membrane sodium channel, Transient Receptor Potential Melastatin Member 4 (TRPM4) as critical for anticancer therapy induced necrosis. TRPM4 knockout in multiple models abolished ErSO-induced ATP depletion, sustained UPR activation, cell swelling, necrotic cell death and increased migration of immune cells. Notably, knockout of TRPM4 completely abolished the ability of ErSO to induce regression of ER positive breast tumors in mice. Supporting a broad role for the TRPM4 pathway in anticancer therapy induced necrosis, rapid cancer cell death induced by four necrosis-inducing cancer therapies unrelated to ErSO, that range from FDA-approved to preclinical, is strongly reversed by TRPM4 knockout. ErSO treatment induces migration of macrophage into regressing tumors. Medium from cancer cells killed by necrosis-inducing ErSO, but not by an apoptosis inducer, dramatically increases macrophage migration and activation, as shown by induction of pro-inflammatory cytokines. This work identifies a protein that plays a pivotal role in the action of diverse anticancer therapies inducing immunogenic necrosis. Since increasing levels of TRPM4 increase sensitivity of breast cancer cells to killing by ErSO, TRPM4 is a novel biomarker whose levels can be used to identify patients most likely to benefit from ErSO and other necrosis-inducing cancer therapies. Citation Format: Santanu Ghosh, Rachel Yang, Darjan Duraki, Ji Eun Kim, Junyao Zhu, Mara Livezey, Matthew Boudreau, Ben H. Park, TImothy Fan, Erik R. Nelson, Paul J. Hergenrother, David J. Shapiro. The Executioner Protein for Immunogenic Anticancer Drug-induced Necrosis in ER Positive Breast Cancer is Transient Receptor Potential Melastatin Member 4 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-01.

Many recent studies have shown that joint-resident mesenchymal stem cells (MSCs) play a vital role in articular cartilage (AC) in situ regeneration. Specifically, synovium-derived MSCs (SMSCs), which have strong chondrogenic differentiation potential, may be the main driver of cartilage repair. However, both the insufficient number of MSCs and the lack of an ideal regenerative microenvironment in the defect area will seriously affect the regeneration of AC. Tetrahedral framework nucleic acids (tFNAs), notable novel nanomaterials, are considered prospective biological regulators in biomedical engineering. Here, we aimed to explore whether tFNAs have positive effects on AC in situ regeneration and to investigate the related mechanism. The results of in vitro experiments showed that the proliferation and migration of SMSCs were significantly enhanced by tFNAs. In addition, tFNAs, which were added to chondrogenic induction medium, were shown to promote the chondrogenic capacity of SMSCs by increasing the phosphorylation of Smad2/3. In animal models, the injection of tFNAs improved the therapeutic outcome of cartilage defects compared with that of the control treatments without tFNAs. In conclusion, this is the first report to demonstrate that tFNAs can promote the chondrogenic differentiation of SMSCs in vitro and enhance AC regeneration in vivo, indicating that tFNAs may become a promising therapeutic for AC regeneration., Graphical abstract Image 1, Highlights • Tetrahedral framework nucleic acids (tFNAs) can promote SMSCs proliferation by activating the Wnt/β-catenin pathway. • tFNAs can promote SMSCs migration in vitro and vivo. • tFNAs can promote SMSCs chondrogenic differentiation by regulating the TGF/Smad2/3 signaling pathway. • tFNAs show improved articular cartilage in situ regeneration activity in vivo.

Gouty arthritis is a very familiar inflammatory arthritis. Controlling inflammation is the key to preventing gouty arthritis. However, colchicine, the most highly represented drug used in clinical practice, has strict contraindications owing to some severe side effects. Curcumin (Cur), a natural anti-inflammatory drug, has demonstrated good safety and efficacy. However, the rapid degradation, poor aqueous solubility, and low bioavailability of Cur limit its therapeutic effect. To strengthen the effectiveness and bioavailability of Cur. Cur loaded tetrahedral framework nucleic acids (Cur-TFNAs) were synthesized to deliver Cur. Compared with free Cur, Cur-TFNAs exhibit a preferable drug stability, good biocompatibility (CCK-8 assay), ease of uptake (immunofluorescence), and higher tissue utilization (in vivo biodistribution). Most importantly, Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression. Therefore, we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases., Graphical abstract Schematic illustration of treating acute gouty arthritis with Cur loaded TFNAs. Cur-TFNAs were absorbed by inflammatory RAW264.7 cells and inhibited the activation of NF-κB, which decreased the levels of ROS, NO and inflammatory factors (IL-6, IL-1β and TNF-α), thus affecting the progression of acute gouty arthritis.Image 1, Highlights • The drug curcumin system based on DNA nanostructures (Cur-TFNAs) were developed to obtain a novel nanomaterial with high water solubility, large encapsulation efficiency, sustained drug release and excellent drug stability. • Based on cellular uptake and in vivo drug imaging, Cur-TFNAs improve the retention of Cur in cells and tissues. • Cur-TFNAs prevent acute gouty arthritis through mediating anti-inflammatory and antioxidant responses of macrophage.

Three oxidants (sodium hypochlorite [NaClO], ozone, and ultraviolet rays) were combined with powdered activated carbon (PAC) and ultrafiltration (UF) for advanced treatment of the secondary effluen...

As an effective targeted therapy for advanced hepatocellular carcinoma (HCC), sorafenib resistance has been frequently reported in recent years, with the activation of autophagy by cancer cells under drug stress being one of the crucial reasons. Sorafenib treatment could enhance autophagy in HCC cells and autophagy is also considered as an important mechanisms of drug resistance. Therefore, the inhibition of autophagy is a potential way to improve the sensitivity and eliminate drug resistance to restore their efficacy. To determine whether autophagy is involved in sorafenib resistance and investigate its role in the regulation of HepG2 cells’ (an HCC cell line) chemosensitivity to sorafenib, we simultaneously treated HepG2 with sorafenib and 3-Methyladenine (3-MA) (a common autophagy inhibitor). First, by performing cell counting kit 8 cell viability assay, Hoechst 33342 apoptosis staining, and Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis kit detection, we found that both sorafenib and 3-MA effectively inhibitted the proliferative activity of HepG2 cells and induced their apoptosis to a certain extent. This effect was significantly enhanced after these two drugs were combined, which was also confirmed by the increased expression of apoptosis-related proteins. Subsequently, by using AAV-GFP-LC3 transfection methods and transmission electron microscopy, we found that both the number and activity of autophagosomes in HepG2 cells in sorafenib and 3-MA group were significantly reduced, suggesting that autophagy activity was inhibited, and this result was consistent with the expression results of autophagy-related proteins. Therefore, we conclude that 3-MA may attenuate the acquired drug resistance of sorafenib by counteracting its induction of autophagy activity, thus enhancing its sensitivity to advanced HCC therapy.

BackgroundThe outbreak of coronavirus disease (COVID-19) poses a great threat to global public health. At present, the number of newly confirmed COVID-19 cases and deaths is increasing worldwide. The strategy of comprehensive and scientific detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through quantitative real-time polymerase chain reaction (qRT-PCR) for special populations and environments provides great support for the prevention and control of this pandemic in China. Our study focused on determining the factors associated with the length of time from symptom onset to the first positive nucleic acid test of throat swabs in COVID-19 patients, evaluating the effect of early positive nucleic acid detection on the disease severity and its significance in prognosis, and predicting the factors associated with the time from positive SARS-CoV-2 RNA test to negative conversion (negative conversion of SARS-CoV-2 virus) in COVID-19 patients.MethodsThis study included 116 hospitalized patients with COVID-19 from January 30, 2020 to March 4, 2020 in Wuhan, China. Throat swab samples were collected for qRT-PCR testing of SARS-CoV-2 RNA, and all patients included in this study were positive for this test.ResultsThe multivariate Cox proportional hazards model showed that disease severity (HR = 0.572; 95% CI 0.348–0.942; p = 0.028) was a protective factor for the time from symptom onset to positive nucleic acid detection. Meanwhile, the time from symptom onset to positive nucleic acid detection (HR = 1.010; 95% CI 1.005–1.020; p = 0.0282) was an independent risk factor for the delay in negative conversion time of SARS-CoV-2 virus. However, the severity of the disease (HR=1.120; 95% CI 0.771–1.640; p = 0.544) had no correlation with the negative conversion time of SARS-CoV-2 virus.ConclusionsPatients with more severe disease had a shorter time from symptom onset to a positive nucleic acid test. Prolonged time from symptom onset to positive nucleic acid test was an independent risk factor for the delay in negative conversion time of SARS-CoV-2 virus, and the severity of the disease had no correlation with negative conversion time of SARS-CoV-2 virus.

The challenges associated with muscle degenerative diseases and volumetric muscle loss (VML) emphasizes the prospects of muscle tissue regeneration. Especially, it is essential to maintain the stemness and self-renewal of myoblasts for generating an adequate number of cells as quickly as possible, which highlights the importance of the quantity and quality of myoblasts. However, changes in aged cellular status are gradually manifested due to decline in muscle repair capacity. Currently, in the absence of a satisfactory approach to maintain muscle regeneration capacity, the discovery of drugs for promoting myoblast activity in muscle regeneration remains the goal of experimental research. Tetrahedral framework nucleic acids (tFNAs) can regulate various biological behaviors of cells, including proliferation and migration, which imply a great potential in tissue engineering. In the present study, we investigated the effects of tFNAs on proliferation, autophagy regulation, stemness maintenance, and associated potential mechanism of myoblasts, and their skeletal muscle repairment in vivo. Our results revealed that tFNAs promoted the proliferation of myoblasts via the Wnt/β-catenin signal pathway. Moreover, the autophagy level of myoblasts was upregulated and the stemness was also maintained upon exposure to tFNAs. Further, the animal experiments demonstrated that tFNAs could accelerate skeletal muscle regeneration in acute muscle injury. Therefore, a new idea for enhancing myoblast activity and promoting skeletal muscle regeneration based on the application of tFNAs is provided.

For decades, an on-going concerted effort has been made to develop a universal DNA vaccine to combat the looming threat of a potential outbreak of the emerging Japanese encephalitis virus (JEV) infection. However, effective strategies are urgently required to counter poor immunogenicity and insufficient long-term protection. Recent reports have confirmed the critical role of autophagy in antigen presentation, long-term immune memory and immune responses against JEV. In this study, JEV prM and E protein with strong immunogenicity were fused with microtubule-associated protein 1 light chain 3 (LC3) encoding gene to construct an autophagy-mediated pJME-LC3 DNA vaccine. Researches indicated significant increase of autophagosomes or LC3 Ⅱ expression in pJME-LC3 transfected cells. Furthermore, prME-LC3 fused protein was observed co-localized with GFP-LC3 to autophagosomes, which means it was successfully targeted to autophagosomes. After immunizing with pJME-LC3, mice were detected highest proportion of CD3+CD8+ T lymphocytes, CD8+ effector memory T cells (TEMs) and JEV specific cytotoxic T lymphocyte (CTL) activity to eliminate JEV. pJME-LC3 also enhanced IgG2a antibody in serum and cytokines IFN-γ, IL-12 produced by splenocytes, thus skew toward Th1 type immune response by activating the JAK2/STAT1 signaling pathway and upregulating expression of transcription factor T-bet. Notably, mice immunized with pJME-LC3 showed highest survival rate and long-lasting neutralizing antibody when challenged with virulent JEV, which were consistent with augment in percentage of CD4+ central memory T cells (TCMs). In brief, our studies suggested that autophagy can be used as a optimization strategy to enhance JEV specific immune response and long-term immune memory. Our attempt will contribute towards future efforts to develop an efficacious JEV vaccine.

Acute myocardial infarction, which can be extremely difficult to treat, is the worst deadly disease around the world. Reperfusion is expedient to reverse myocardial ischemia. However, during reperfusion, reactive oxygen species (ROS) produced by myocardial ischemia-reperfusion injury (MIRI) and further cell apoptosis are the most serious challenges to cardiomyocytes. Therefore, searching for reagents that can simultaneously reduce oxidative damage and MIRI-induced apoptosis is the pivotal strategy to rescue injured cardiomyocytes. Nevertheless, current cardioprotective drugs have some shortcomings, such as cardiotoxicity, inadequate intravenous administration, or immature technology. Previous studies have shown that tetrahedral DNA nanostructures (TDNs) have biological safety with promising anti-inflammatory and antioxidative potential. However, the progress that TDNs have made in the biological behavior of cardiomyocytes has not been explored. In this experiment, a cellular model of MIRI was first established. Then, confirmed by a series of experiments, our study indicates that TDNs can significantly decrease oxidative damage and apoptosis by limiting the overexpression of ROS, along with effecting the expression of apoptosis-related proteins. In addition, Western blot analysis demonstrated that TDNs could activate the Akt/Nrf2 signaling pathway to improve the myocardial injury induced by MIRI. Above all, the antioxidant and antiapoptotic capacities of TDNs make them a potential therapeutic drug for MIRI. This study provides new ideas and directions for more homogeneous diseases induced by oxidative damage.

Retinal ischemia-reperfusion (I/R) injuries are involved in the universal pathological processes of many ophthalmic diseases, including glaucoma, diabetic retinopathy, and retinal arterial occlusion. The reason is that the ischemia-reperfusion injury is accompanied by the abnormal accumulation of reactive oxygen species (ROS), which can cause damage to retinal ganglion cells (RGCs), promote their apoptosis, and finally lead to the irreversible loss of the visual field. RGCs are specialized projection neurons that are situated in the inner retinal surface of the eye, and they transmit visual images into certain areas of the brain in the form of action potentials. Therefore, any damage that affects the viability of RGCs can cause visual field defects or even irreversible vision loss. There is no effective drug treatment in clinical practice for the loss of the visual field that is caused by the oxidation and apoptosis of RGCs. Hence, finding a drug with neuroprotective and antioxidant functions is urgently needed. As a new type of nanomaterial, tetrahedral framework nucleic acids (tFNAs) exhibit outstanding biocompatibility and have been shown in our previous studies to participate in the positive regulation of cell behavior. In this experiment, we first established a cellular model of oxidative stress in RGCs with tert-butyl peroxide (TBHP). Then, we primarily explored the antioxidant and neuroprotective effects of tFNAs after TBHP-induced oxidative stress and the main mechanisms by which the tFNAs function. Our research showed that tFNAs could reduce the production of reactive oxygen species (ROS) in cells and protect the cells from oxidative stress by regulating intracellular oxidation-related enzymes. In addition, tFNAs could simultaneously improve oxidative stress-induced apoptosis significantly via affecting the expression of apoptosis-related proteins. Finally, we confirmed by western blotting that the mechanism by which tFNAs prevent damage caused by oxidative stress involves activating the Akt/Nrf2 pathway. Our findings provide new ideas for the prevention and treatment of a series of diseases that are caused by oxidative stress to RGCs.

While the skin is considered the first line of defense in the human body, there are some vulnerabilities that render it susceptible to certain threats, which is an issue that is recognized by both patients and doctors. Cutaneous wound healing is a series of complex processes that involve many types of cells, such as fibroblasts and keratinocytes. This study showed that tetrahedral framework nucleic acids (tFNAs), a type of self-assembled nucleic-acid material, have the ability to promote keratinocyte(HaCaT cell line) and fibroblast(HSF cell line) proliferation and migration in vitro. In addition, tFNAs increased the secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in HSF cells and reduced the production of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in HaCaT cells by activating the AKT-signaling pathway. During in vivo experiments, tFNA treatments accelerated the healing process in skin wounds and decreased the development of scars, compared with the control treatment that did not use tFNAs. This is the first study to demonstrate that nanophase materials with the biological features of nucleic acids accelerate the healing of cutaneous wounds and reduce scarring, which indicates the potential application of tFNAs in skin tissue regeneration.

Zoledronic acid (ZA) is a bisphosphonate (BP) drug that has been widely used in clinical treatments as a potent bone resorption inhibitor. In recent years, an increasing number of cases of bisphosphonate-associated osteonecrosis of the jaw (BRONJ) have been reported. This is a severe maxillofacial complication characterized clinically by bone exposure, necrosis, pain, and halitosis. Its pathogenesis is still not clear, and there is no effective clinical treatment known. Therefore, prevention of BRONJ is especially important. To provide a new research direction for the treatment of BRONJ, this study used a new tetrahedral framework nucleic acid (TFNA), which can antagonize the inhibitory effect of ZA on the differentiation and maturation of osteoclasts (OCs). In vivo and in vitro experiments showed that TFNAs at a specific concentration exhibited no cytotoxicity and could reverse the inhibition of ZA on OC differentiation and maturation, effectively inhibiting the formation of BRONJ.

Background & aims Emerging evidence supports ambient fine particulate matter (PM2.5) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM2.5 exposure and investigate the underlying mechanism by which PM2.5 modulates hepatic lipid metabolism. Methods Both male and female C57BL/6 mice were randomly assigned to ambient PM2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatography-mass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM2.5 exposure-induced metabolic disorder. Results Female mice were more susceptible than their male counterparts to ambient PM2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM2.5-exposed mice as well. In addition, exposure to PM2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM2.5-induced metabolic dysfunction. Conclusions Ambient PM2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.

Additional file 1: Supplemental Materials. Supplemental Figure 1. Body weight and fasting blood glucose before PM2.5 exposure in C57BL/6 mice. A, Absolute value of body weight. B, Absolute value of fasting blood glucose. C, Fold change of body weight relative to FA. D, Fold change of blood glucose relative to FA. n=8. Supplemental Figure 2. Effects of PM2.5 exposure on body weight and glucose homeostasis in C57BL/6 mice at the end of PM2.5 exposure. A, Fold change of body weight relative to FA. B, Fold change of fasting blood glucose relative to FA. C-D, Fold change of fasting insulin levels (C) and HOMA-IR (D). E, Fold change of AUC (area under curves) of ITT relative to FA. *P

Multiple sclerosis (MS) is one of the most famous and common demyelinating diseases in young adults, characterized by motor, sensory, and cognitive impairments. In MS patients, multifocal demyelinating lesions, inflammatory infiltrates, axonal damage, and deletion of oligodendrocytes are observed. For the solely immunomodulatory focus has exhibited unsatisfactory ability to combat the progression of MS disability. There is an absence of first-line drugs against MS to delay the progression and obtain clinical improvement. Tetrahedral framework nucleic acids (tFNAs), novel self-assembled nucleic-acid nanomaterials, have been found to exhibit broad application value. Previous studies have reported positive reactions between tFNAs and various cell types, and tFNAs are able to act the advantages of neuroprotective, anti-apoptosis and anti-inflammatory. To investigate a new research direction for remyelination and potential mechanism for MS therapies, we attempted to characterize the effects of tFNAs on remyelination. The results in vitro demonstrated that tFNAs were able to rescue oligodendroglial progenitor cells (OPCs) from interferon-γ (IFN-γ) induced cell death. In in vivo study, functional remyelination was assessed by behavior test and histological examination in cuprizone-induced mice treated with tFNAs. The tFNAs-treated groups exhibited excellent remyelination. Proteins related to the PI3K-AKT-mTOR and mitochondrial apoptotic pathways were examined to further support this finding. In conclusion, our study suggested the therapeutic potential of tFNAs for MS patients by enhancing the remyelination.

Parkinson's disease (PD) is a neurodegenerative disease characterized by a series of progressive motor disorders. PD is caused by dysfunction of basal ganglia, decrease of dopaminergic neurons in substantia nigra, and abnormal accumulation of Lewy bodies and Lewy neurites. Antiparkinsonian agents, which are currently used for treatment of PD, exhibit unsatisfactory effects on disease control. In recent years, tetrahedral framework nucleic acids (TFNAs) have been considered as multifunctional nanomaterials, and their scope of application has been extended to a wide range of areas. In previous studies, TFNAs were shown to exert positive effects on various cell types in processes such as cell proliferation, cell differentiation, and apoptosis. In the present study, we explored the role of TFNAs in the treatment and prevention of PD in vitro and elucidated its underlying mechanisms of action. On the basis of the experiments conducted, we demonstrated that TFNAs could inhibit and repair the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of PC12 cells through decreasing the accumulation of α-synuclein, one of the characteristic biomarkers of PD. Genes and proteins related to the AKT/PI3K signaling and mitochondrial apoptotic pathways were examined to further support this finding. Most importantly, TFNAs exhibited unexpected neuroprotective and neurorestorative effects on PC12 cells, providing a novel approach for reducing the neuropathological changes caused by PD.

In order to ensure the normal operation of mechanical system and solve the problems of complex structure and insufficient cognition caused by mechanical system updating, the advantages of applying augmented reality technology in the field of fault diagnosis and maintenance are analyzed. Firstly, this paper summarizes the application of augmented reality technology for maintenance assistance cases at home and abroad, analyzes its industry characteristics and application advantages, then summarizes the key technologies of augmented reality, and finally prospects the development trend of the system application.

Nitric oxide functions as an important signalling molecule in many biological systems. Nanodiamonds (NDs) have attracted enormous attention in the field of biomaterial science for biosensing applications and drug/gene delivery. In this work, one novel Cu(II)-based rhodamine B probe for NO detection was composed which was covalently bound to the nanodiamond (ND) surface. The results showed that the covalently conjugated ND probe could detect Cu2+ and NO sequentially with high sensitivity, high stability and good reusability compared to a free rhodamine B probe in CH3CN/HEPES (pH 6.8, v/v, 1 : 1). The detection limit for NO was estimated to be 10.5 nM. In addition, the response to NO was reversible in the presence of O3, which has attracted attention in the fields of biology and environmental science. Further analysis of confocal fluorescence microscopy images and the MTT assay indicated that the conjugated ND probe has favorable biocompatibility and low toxicity. This new Cu2+ and NO selective fluorescent ND probe may have potential applications in environmental science and biology.

As a type of novel biomaterial, DNA nanomaterial has been widely applied to biomedical area due to its self-assembly properties. Meanwhile, fibrotic diseases are common health problems, which can lead to multiple organs dysfunction and even death if without proper intervention and treatment. Therefore, we aim to develop the nucleic acids based tetrahedral framework DNA nanostructures (TFNAs) for the treatment of fibrotic diseases. Four single-strand DNA were self-assembled to form tetrahedral framework DNA nanostructures and the anti-fibrotic effects of TFNAs were investigated with an in vitro TGF-β1-induced fibrotic model. TFNAs were successfully assembled and showed obvious cellular uptake. After TFNAs treatment, ROS overproduction, fibrosis-related biomolecules expression including collagen I, fibronectin and α-SMA were obviously reduced. DNA-based TFNAs could be promising biomaterials for the treatment of fibrotic diseases.

From the viewpoint of application, the temperature stability of the electrical properties of the lead-free piezoelectric ceramics is very important. Therefore, it is important to study the temperature stability of the electrical properties of perovskite Bi 0.5 Na{0.5}TiO 3 (BNT)- and K 0.5 Na 0.5 NbO 3 (KNN)-based (Bi 0.47 Na 0.47 )Ba 0.06 TiO 3 (BNBT6) and (K 0.49 Na 0.49 )Li 0.02 Nb 0.95 Sb 0.05 O 3 (KNLNS2-5) were selected, and the temperature stability of the dielectric, piezoelectric, and ferroelectric properties of the two kinds of ceramics were compared from the point of view of the application of the ceramics. It was found that the piezoelectric properties of KNLNS2-5 ceramics are much more stable in the orthorhombic phase than in the tetragonal phase. This is an important clue to obtain excellent piezoelectric properties along with good temperature stability for KNN-based ceramics.

0.95(K 0.48 Na 0.52 NbO 3 )-0.05(LiSbO 3 ) (95KNN-5LS) thin films have been fabricated by pulsed laser deposition (PLD) on Pt/Ti/SiO 2 /Si substrates. The K-rich in the target and the fabrication parameters on the properties of the films was investigated. The results show that good films can be obtained with the 0.95(K 0.48 Na 0.52 NbO 3 )-0.05(LiSbO 3 )-0.0228K 2 CO 3 (95KNN-5LS-4.56K) target, and the surface roughness, film orientation, composition and properties of the films are strongly dependent on the oxygen pressure and oblique angle from the plume axial direction in PLD process.

The new lead-free ferroelectrics with composition of 0.995[(K 0.5 Na 0.5 ) 0.95 Li 0.05 ](Nb 0.95 Sb 0.05 )O 3 -0.005BaTiO 3 (0.995KNLNS-0.005BT) were prepared by using normal sintering method, and the ferroelectric relaxor behavior and electrical properties of the ceramics were systematically studied. The ceramics exhibit typical ferroelectric relaxor behavior, that is, the dielectric peaks become increasingly broad, and the temperature of the maximum dielectric constant is shifted to higher temperature with the increasing frequency. The dielectric relaxor behavior follows the modified Curie-Weiss law. The relaxor behavior of the ceramics should be attributed to the cationic disorder induced by both of the A-sites and B-sites substitutions. The 0.995KNLNS-0.005BT ceramics also exhibit good piezoelectric properties with d 33 of 269 pC/N, k p of 0.50, ɛ r of 1371, tan δ of 0.03, T C of 349 °C, P r of 22.4 µC/cm2, and E c =15.3 kV/cm.

Lead-free piezoelectric buzzers based on (K 0.975 Li 0.025 Na 0.5 )Nb 0.95 Sb{0.05}O 3 (KLNNS2.5-5) ceramics were fabricated and their properties were investigated. The KLNNS2.5-5 ceramics membranes with diameter of 15–16mm and thickness of 0.10–0.11 mm were prepared by the roll forming process. The electrical properties of the lead-free piezo-ceramic membranes are k p =0.445, d 33 =150 pC/N, ɛ r =466 (at 1kHz), and tan δ=0.033 (at 1 kHz). The resonance frequency (f r ) of the super-thin buzzer disks is about 4.68 kHz. The sound pressure level (SPL) of the KLNNS2.5-5 buzzers reaches 84.2 dB at 2 kHz, which are comparable to that of the lead-based ones. The electro-acoustic properties of the KLNNS2.5-5 buzzers can basically satisfy the requirements (⩾ 80 dB) of microwave ovens applications. Results show that the KLNNS2.5-5 ceramics are promising candidates for practical application in buzzers.

0.99[(Na x K 1-x )Nb 0.955 O 3 -0.045LiSbO 3 ]-0.01CaTiO 3 (NKNLS-CT) lead-free piezoelectric ceramics have been prepared by the conventional mixed oxide method. The effect of the K/Na ratio on the electrical properties of NKNLS-CT ceramics was investigated. When x = 0.52, the ceramics possess optimum properties: piezoelectric constant d 33 =266 pC/N, planar electromechanical coupling factors k p =48.7 %. These results show that the NKNLS-CT ceramics may be regarded as the promising lead-free piezoelectric materials.

Lead-free piezoelectric ceramics 0.96(K 0.5 Na 0.5 )(Nb 0.96 Sb 0.04 )-0.04LiTaO 3 (96KNNS-4LT) have been prepared by using the conventional technique. The effect of the sintering temperature on the piezoelectric properties of 96KNNS-4LT ceramics was studied. The X-ray diffraction (XRD) and scanning electron microscope (SEM) show that all the ceramics possess a pure perovskite phase and dense microstructure. The ceramics sintered at 1090 °C show better piezoelectric properties: d 33 =315.5 pC/N, k p =0.455, and T C =348 °C, the optimized sintering temperature range is very narrow for KNN-based ceramics, and the optimized sintering temperature range in which the d 33 and k p are in the range of 0.9 times the maximum one is less than 20 °C. From the results obtained it was pointed out that the sintering temperature is a very critical factor for the K 0.5 Na 0.5 NbO 3 -based lead-free piezoelectric ceramics.

Co doping CdS nanocrystals were synthesized in aqueous solution using mercaptoacetic acid as stabilizer. The prepared nanocrystals were examined using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), fourier transform infrared (FTIR) and UV-vis absorption spectroscopy (ABS). The cubic zinc blende nanocrystals were determined and the sizes were estimated by XRD. The compositions of the nanocrystals was confirmed by XPS, the resultes indiacated that Co2+ existed in the as-prepared nanocrystal. FTIR indicated that the doped as well as undoped nanocrystals were capped by mercaptoacetic acid molecules. Ultraviolet-visible absorption spectra indicated that Co2+ is located at the surface of the nanocrysatles.