Enhanced Hippocampus-Nidopallium Caudolaterale Interaction in Visual-Spatial Associative Learning of Pigeons.

Learning the spatial location associated with visual cues in the environment is crucial for survival. This ability is supported by a distributed interactive network. However, it is not fully understood how the most important task-related brain areas in birds, the hippocampus (Hp) and the nidopallium caudolaterale (NCL), interact in visual-spatial associative learning. To investigate the mechanisms of such coordination, synchrony and causal analysis were applied to the local field potentials of the Hp and NCL of pigeons while performing a visual-spatial associative learning task. The results showed that, over the course of learning, theta-band (4-12 Hz) oscillations in the Hp and NCL became strongly synchronized before the pigeons entered the critical choice platform for turning, with the information flowing preferentially from the Hp to the NCL. The learning process was primarily associated with the increased Hp-NCL interaction of theta rhythm. Meanwhile, the enhanced theta-band Hp-NCL interaction predicted the correct choice, supporting the pigeons' use of visual cues to guide navigation. These findings provide insight into the dynamics of Hp-NCL interaction during visual-spatial associative learning, serving to reveal the mechanisms of Hp and NCL coordination during the encoding and retrieval of visual-spatial associative memory.

Performance Baseline of Phase Transfer Entropy Methods for Detecting Animal Brain Area Interactions.

Objective: Phase transfer entropy (TEθ) methods perform well in animal sensory-spatial associative learning. However, their advantages and disadvantages remain unclear, constraining their usage. Method: This paper proposes the performance baseline of the TEθ methods. Specifically, four TEθ methods are applied to the simulated signals generated by a neural mass model and the actual neural data from ferrets with known interaction properties to investigate the accuracy, stability, and computational complexity of the TEθ methods in identifying the directional coupling. Then, the most suitable method is selected based on the performance baseline and used on the local field potential recorded from pigeons to detect the interaction between the hippocampus (Hp) and nidopallium caudolaterale (NCL) in visual-spatial associative learning. Results: (1) This paper obtains a performance baseline table that contains the most suitable method for different scenarios. (2) The TEθ method identifies an information flow preferentially from Hp to NCL of pigeons at the θ band (4-12 Hz) in visual-spatial associative learning. Significance: These outcomes provide a reference for the TEθ methods in detecting the interactions between brain areas.

Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy-Induced Necrosis.

Several emerging therapies kill cancer cells primarily by inducing necrosis. As necrosis activates immune cells, potentially, uncovering the molecular drivers of anticancer therapy-induced necrosis could reveal approaches for enhancing immunotherapy efficacy. To identify necrosis-associated genes, we performed a genome-wide CRISPR-Cas9 screen with negative selection against necrosis-inducing preclinical agents BHPI and conducted follow-on experiments with ErSO. The screen identified transient receptor potential melastatin member 4 (TRPM4), a calcium-activated, ATP-inhibited, sodium-selective plasma membrane channel. Cancer cells selected for resistance to BHPI and ErSO exhibited robust TRPM4 downregulation, and TRPM4 reexpression restored sensitivity to ErSO. Notably, TRPM4 knockout (TKO) abolished ErSO-induced regression of breast tumors in mice. Supporting a broad role for TRPM4 in necrosis, knockout of TRPM4 reversed cell death induced by four additional diverse necrosis-inducing cancer therapies. ErSO induced anticipatory unfolded protein response (a-UPR) hyperactivation, long-term necrotic cell death, and release of damage-associated molecular patterns that activated macrophages and increased monocyte migration, all of which was abolished by TKO. Furthermore, loss of TRPM4 suppressed the ErSO-induced increase in cell volume and depletion of ATP. These data suggest that ErSO triggers initial activation of the a-UPR but that it is TRPM4-mediated sodium influx and cell swelling, resulting in osmotic stress, which sustains and propagates lethal a-UPR hyperactivation. Thus, TRPM4 plays a pivotal role in sustaining lethal a-UPR hyperactivation that mediates the anticancer activity of diverse necrosis-inducing therapies. SIGNIFICANCE: A genome-wide CRISPR screen reveals a pivotal role for TRPM4 in cell death and immune activation following treatment with diverse necrosis-inducing anticancer therapies, which could facilitate development of necrosis-based cancer immunotherapies.

Slow filtration operating conditions for the removal of opportunistic pathogens in a secondary effluent.

The secondary effluent of urban sewage treatment plants contains many opportunistic pathogens (OPs), which pose a potential threat to human health. In this study, the slow filtration technique is employed as the advanced treatment procedure, with the secondary effluent as the treatment object. The effectiveness of the operating conditions of the slow filtration process (filtration rate and Ca2+ concentration) in removing OPs (Pseudomonas aeruginosa, Legionella and Mycobacterium avium) and Escherichia coli from water, as well as the dynamic deposition process of pollutants on the surface of the slow filtration biofilm, was investigated. The results showed that under different filtration rates and different Ca2+ concentrations, biofilm slow filtration was more effective in removing OPs than slow filtration. The optimal filtration rate of biofilm slow filtration was 5 cm/h, and the optimal inlet Ca2+ concentration was 60 mg/L. When the filtration rate was 5 cm/h, the deposition of pollutants in the secondary effluent on the surface of biofilm slow filtration was mainly dominated by the physical adhesion of extracellular polymeric substances (EPS). When the concentration of Ca2+ was 60 mg/L, the adsorption of microorganisms was the primary method.

Goal given moment modulates the time period of gamma oscillations in nidopallium caudolaterale during the goal-directed behavior of pigeon.

The cognitive processes of goal-directed navigation are believed to be organized around and serve the identification and selection of goals. Differences in LFP signals in avian nidopallium caudolaterale (NCL) under different goal location/distance information in the goal-directed behavior have been studied. However, for goals that are multifarious constructs that include various information, the modulation of goal time information on the LFP of NCL during goal-directed behavior remains unclear. In this study, we recorded the LFP activity from the NCL of eight pigeons as they performed two goal-directed decision-making tasks in a plus-maze. During the two tasks with different goal time information, spectral analysis revealed significant LFP power selectively enhanced in the slow gamma band (40-60 Hz), while the slow gamma band of LFP which could effectively decode the behavioral goal of the pigeons existed in different time periods. These findings suggest that the LFP activity in the gamma band correlates with the goal-time information, and help to shed light on the contribution of the gamma rhythm recorded from the NCL in goal-directed behavior.

A Fast and Efficient Ensemble Transfer Entropy and Applications in Neural Signals.

The ensemble transfer entropy (TEensemble) refers to the transfer entropy estimated from an ensemble of realizations. Due to its time-resolved analysis, it is adapted to analyze the dynamic interaction between brain regions. However, in the traditional TEensemble, multiple sets of surrogate data should be used to construct the null hypothesis distribution, which dramatically increases the computational complexity. To reduce the computational cost, a fast, efficient TEensemble with a simple statistical test method is proposed here, in which just one set of surrogate data is involved. To validate the improved efficiency, the simulated neural signals are used to compare the characteristics of the novel TEensemble with those of the traditional TEensemble. The results show that the time consumption is reduced by two or three magnitudes in the novel TEensemble. Importantly, the proposed TEensemble could accurately track the dynamic interaction process and detect the strength and the direction of interaction robustly even in the presence of moderate noises. The novel TEensemble reaches its steady state with the increased samples, which is slower than the traditional method. Furthermore, the effectiveness of the novel TEensemble was verified in the actual neural signals. Accordingly, the TEensemble proposed in this work may provide a suitable way to investigate the dynamic interactions between brain regions.

The Value of Early Positive Nucleic Acid Test and Negative Conversion Time of SARS-CoV-2 RNA in the Clinical Outcome of COVID-19 Patients.

Background: The 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. Methods: This 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. Results: The 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. Conclusions: Patients 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 Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases.

For decades, it has been widely believed that the blood-brain barrier (BBB) provides an immune privileged environment in the central nervous system (CNS) by blocking peripheral immune cells and humoral immune factors. This view has been revised in recent years, with increasing evidence revealing that the peripheral immune system plays a critical role in regulating CNS homeostasis and disease. Neurodegenerative diseases are characterized by progressive dysfunction and the loss of neurons in the CNS. An increasing number of studies have focused on the role of the connection between the peripheral immune system and the CNS in neurodegenerative diseases. On the one hand, peripherally released cytokines can cross the BBB, cause direct neurotoxicity and contribute to the activation of microglia and astrocytes. On the other hand, peripheral immune cells can also infiltrate the brain and participate in the progression of neuroinflammatory and neurodegenerative diseases. Neurodegenerative diseases have a high morbidity and disability rate, yet there are no effective therapies to stop or reverse their progression. In recent years, neuroinflammation has received much attention as a therapeutic target for many neurodegenerative diseases. In this review, we highlight the emerging role of the peripheral and central immune systems in neurodegenerative diseases, as well as their interactions. A better understanding of the emerging role of the immune systems may improve therapeutic strategies for neurodegenerative diseases.

Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis.

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.

Tetrahedral framework nucleic acids promote the biological functions and related mechanism of synovium-derived mesenchymal stem cells and show improved articular cartilage regeneration activity in situ.

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.

The Emerging Role of Ferroptosis in Liver Diseases.

Ferroptosis is a newly discovered type of cell death mediated by iron-dependent lipid peroxide. The disturbance of iron metabolism, imbalance of the amino acid antioxidant system, and lipid peroxide accumulation are considered distinct fingerprints of ferroptosis. The dysregulation of ferroptosis has been intensively studied in recent years due to its participation in various diseases, including cancer, kidney injury, and neurodegenerative diseases. Notably, increasing evidence indicates that ferroptosis plays different roles in a wide spectrum of liver diseases. On the one hand, inhibiting ferroptosis may counteract the pathophysiological progression of several liver diseases, such as alcoholic liver injury, nonalcoholic steatosis hepatitis and fibrosis. On the other hand, inducing ferroptosis may restrict the emergence of secondary resistance to current medicines, such as sorafenib, for hepatocellular carcinoma (HCC) therapy. Here, we summarize the biological characteristics and regulatory signalling pathways of ferroptosis involved in liver disease. The current available medical agents targeting ferroptosis, including inducers or inhibitors applied in liver diseases, are also reviewed. This work aims to provide new insight into the emerging role of pathogenesis and therapeutic approaches for liver diseases.

3-Methyladenine-enhanced susceptibility to sorafenib in hepatocellular carcinoma cells by inhibiting autophagy.

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.

Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway.

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-1ß) 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.

Preventive effect of tetrahedral framework nucleic acids on bisphosphonate-related osteonecrosis of the jaw.

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.

Sex-dependent effects of ambient PM2.5 pollution on insulin sensitivity and hepatic lipid metabolism in mice.

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.

Tetrahedral framework nucleic acids prevent retina ischemia-reperfusion injury from oxidative stress via activating the Akt/Nrf2 pathway.

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.

Enhancement of autophagy as a strategy for development of new DNA vaccine candidates against Japanese encephalitis.

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.

Neuroprotective and Neurotherapeutic Effects of Tetrahedral Framework Nucleic Acids on Parkinson's Disease in Vitro.

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.

Cardioprotection of Tetrahedral DNA Nanostructures in Myocardial Ischemia-Reperfusion Injury.

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.

Application of nanodiamonds in Cu(ii)-based rhodamine B probes for NO detection and cell imaging.

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.