Combining Multiple Photosensitizer Modules into One Supramolecular System for Synergetic Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT), as an emerging cancer treatment, requires the development of highly desirable photosensitizers (PSs) with integrated functional groups to achieve enhanced therapeutic efficacy. Coordination-driven self-assembly (CDSA) would provide an alternative approach for combining multiple PSs synergistically. Here, we demonstrate a simple yet powerful strategy of combining conventional chromophores (tetraphenylethylene, porphyrin, or Zn-porphyrin) with pyridinium salt PSs together through condensation reactions, followed by CDSA to construct a series of novel metallo-supramolecular PSs (S1-S3). The generation of reactive oxygen species (ROS) is dramatically enhanced by the direct combination of two different PSs, and further reinforced in the subsequent ensembles. Among all the ensembles, S2 with two porphyrin cores shows the highest ROS generation efficiency, specific interactions with lysosome, and strong emission for probing cells. Moreover, the cellular and living experiments confirm that S2 has excellent PDT efficacy, biocompatibility, and biosafety. As such, this study will enable the development of more efficient PSs with potential clinical applications.

To Love and to Kill: Accurate and Selective Colorimetry for Both Chloride and Mercury Ions Regulated by Electro-Synthesized Oxidase-like SnTe Nanobelts.

Herein, SnTe nanobelts (NBs) with efficient oxidase-mimetic activity were synthesized by the simple electrochemical exfoliation method. A specific inhibition effect of Cl- on the enzymatic behavior of the pure SnTe NBs was discovered, which was accordingly used for establishing a highly feasible, sensitive, selective, and stable Cl- colorimetric assay. The detection concentration range was 50 nM to 1 mM, and the lowest detection limit was 20 nM for Cl-. In addition, a signal on-off-on route based on the SnTe NB nanozyme was designed to realize the reliable and specific detection of Hg2+. Therein, the SnTe NBs were grafted with gold nanoparticles to form a hybrid of SnTe/Au, resulting in the depression of the oxidase-like activity, which can then be recovered in the presence of the Hg2+ due to the formation of a gold amalgam. Especially, it was found that the high concentration of Cl- over 3 mM could again exert suppression influence toward the enzymatic activity of the SnTe/Au-Hg system. Based on the to-love-and-to-kill interaction between Cl- and Hg2+, the detection range for Cl- can be extended to 40 to 250 mM. In return, the assays of Cl- could avoid in advance its interference toward the accurate Hg2+ assays. We systematically clarified the oxidase-like catalytic mechanism of the SnTe-derived nanozyme systems. The as-proposed colorimetry can be successfully applied in practical samples including the sweat, human serum, or seawater/tap water, relating to cystic fibrosis, hyper-/hypochloremia, or environmental control, respectively.

Near-Infrared Regulated Nanozymatic/Photothermal/Photodynamic Triple-Therapy for Combating Multidrug-Resistant Bacterial Infections via Oxygen-Vacancy Molybdenum Trioxide Nanodots.

Bacterial infections have become a major danger to public health because of the appearance of the antibiotic resistance. The synergistic combination of multiple therapies should be more effective compared with the respective one alone, but has been rarely demonstrated in combating bacterial infections till now. Herein, oxygen-vacancy molybdenum trioxide nanodots (MoO3-x NDs) are proposed as an efficient and safe bacteriostatic. The MoO3-x NDs alone possess triple-therapy synergistic efficiency based on the single near-infrared irradiation (808 nm) regulated combination of photodynamic, photothermal, and peroxidase-like enzymatic activities. Therein, photodynamic and photothermal therapies can be both achieved under the excitation of a single wavelength light source (808 nm). Both the photodynamic and nanozyme activity can result in the generation of reactive oxygen species (ROS) to reach the broad-spectrum sterilization. Interestingly, the photothermal effect can regulate the MoO3-x NDs to their optimum enzymatic temperature (50 °C) to give sufficient ROS generation in low concentration of H2 O2 (100 µm). The MoO3-x NDs show excellent antibacterial efficiency against drug-resistance extended spectrum ß-lactamases producing Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Animal experiments further indicate that the MoO3-x NDs can effectively treat wounds infected with MRSA in living systems.

Determination of Mineral Elements in Nanyang Mugwort (Artemisia argyi) Leaves Harvested from Different Crops by Inductively Coupled Plasma Mass Spectrometry and Inductively Coupled Plasma Atomic Emission Spectrometry.

Due to high need for medical purposes, multiple harvests of mugwort (Artemisia argyi) have been extensively applied in China for the increase of mugwort yield recently. However, the investigation on the mineral elements in different crops, which are significantly related to mugwort growth and the clinical efficacy of this medicinal herb, has not been conducted. This study provided an analytical method and quality evaluation for mineral elements in Nanyang mugwort leaves harvested from three different crops. The contents of 35 mineral elements were determined by inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). ANOVA, principal component analysis and factor analysis were applied to evaluate the results. Four principal components were identified and their comprehensive evaluation function was as follows: F = 0.7008Fl + 0.1236F2 + 0.0936F3 + 0.0321F4. The comprehensive scores of the mugwort leaves from different crops were ranked as follows: 3rd crop > 2nd crop ≈ 1st crop. These findings can provide a reference for the quality control and clinical use of mugwort leaves, and a guidance of differential nourishing strategies for different crops.

Application of a Cascaded Nanozyme in Infected Wound Recovery of Diabetic Mice.

The emergence of peroxidase (POD)-like nanozyme-derived catalytic therapy has provided a promising choice for reactive oxygen species (ROS)-mediated broad-spectrum antibacterials to replace antibiotics, but it still suffers from limitations of low therapeutic efficiency and unusual addition of unstable H2O2. Considering that the higher blood glucose in diabetic wounds provides much more numerous nutrients for bacterial growth, a cascade nanoenzymatic active material was developed by coating glucose oxidase (GOx) onto POD-like Fe2(MoO4)3 [Fe2(MoO4)3@GOx]. GOx could consume the nutrient of glucose to produce gluconic acid (weakly acidic) and H2O2, which could be subsequently converted into highly oxidative •OH via the catalysis of POD-like Fe2(MoO4)3. Accordingly, the synergistic effect of starvation and ROS-mediated therapy showed significantly efficient antibacterial effect while avoiding the external addition of H2O2 that affects the stability and efficacy of the therapy system. Compared with the bactericidal rates of 46.2-59.404% of GOx or Fe2(MoO4)3 alone on extended-spectrum ß-lactamases producing Escherichia coli and methicillin-resistant Staphylococcus aureus, those of the Fe2(MoO4)3@GOx group are 98.396 and 98.776%, respectively. Animal experiments showed that the as-synthesized Fe2(MoO4)3@GOx could much efficiently promote the recovery of infected wounds in type 2 diabetic mice while showing low cytotoxicity in vivo.

IPR-based distributed interval observers design for uncertain LTI systems.

This paper designs a novel distributed interval observer for Linear Time Invariant (LTI) systems with additive disturbances. The technique of observer construction relies on the Internal Positive Representations (IPRs) of systems and synchronizing region approach, which ensures that the error system is stably and positive. Each observer estimates the upper and lower bounds (ULBs) of the system states by only using part of the output information and the information interaction with their neighbors. Numerical examples are simulated to demonstrate the effectiveness of the proposed approach.

Event-triggered controller design for LTI systems: A distributed interval observer-based approach.

This paper investigates the distributed event-triggered control design problem for networked linear time-invariant (LTI) systems with partially measurable states, in the presence of bounded external disturbances. A distributed interval observer-based event-triggered control scheme has been proposed, the main features of this scheme lie in a) designing a novel distributed interval observer to deal with the unknown states and bound disturbances problem; b) proposing a distributed feedback control method using interval estimation information, the partially measurable limitation has been solved; c) introducing a decreased time-varying function with dead-zone modification to avoid the Zeno behavior. Moreover, sufficient conditions for the stability of closed-loop systems are given in the Lyapunov sense by using matrix inequalities and transmission strategy. Finally, the uniformly ultimately bounded stability and Zeno behavior avoidance of the proposed approach have been numerically demonstrated.

NIR-II Aggregation-Induced Emission Luminogens for Tumor Phototheranostics.

As an emerging and powerful material, aggregation-induced emission luminogens (AIEgens), which could simultaneously provide a precise diagnosis and efficient therapeutics, have exhibited significant superiorities in the field of phototheranostics. Of particular interest is phototheranostics based on AIEgens with the emission in the range of second near-infrared (NIR-II) range (1000-1700 nm), which has promoted the feasibility of their clinical applications by virtue of numerous preponderances benefiting from the extremely long wavelength. In this minireview, we summarize the latest advances in the field of phototheranostics based on NIR-II AIEgens during the past 3 years, including the strategies of constructing NIR-II AIEgens and their applications in different theranostic modalities (FLI-guided PTT, PAI-guided PTT, and multimodal imaging-guided PDT-PTT synergistic therapy); in addition, a brief conclusion of perspectives and challenges in the field of phototheranostics is given at the end.

The Antibacterial Potential of Ciprofloxacin Hybrids against Staphylococcus aureus.

Staphylococcus aureus (S. aureus), an important pathogen of both humans and animals, can cause a variety of infections at any site of the body. The evolution of S. aureus resistance is notorious, and the widespread of drug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA), has made the treatment difficult in recent decades. Nowadays, S. aureus is among the leading causes of bacterial infections, creating an urgent need for the development of novel antibacterial agents. Ciprofloxacin, characterized by high clinical efficacy, is a broad-spectrum antibacterial agent with frequency of prescription for various Gram-positive and Gram-negative pathogens, many of which are resistant to a wide range of antibiotics. However, the long-term and widespread use of this antibiotic has led to the emergence of ciprofloxacin-resistant pathogens, and ciprofloxacin- resistant S. aureus has been noted in clinical practice. Ciprofloxacin hybrids have been recognized as advanced chemical entities to simultaneously modulate multiple drug targets in bacteria, so ciprofloxacin hybrids have the potential to overcome drug resistance. The present review provides an overview of ciprofloxacin hybrids with anti-S. aureus potential that has been reported in the last decade with an emphasis on their structure-activity relationships and mechanisms of action.

Type I Photosensitizers Based on Aggregation-Induced Emission: A Rising Star in Photodynamic Therapy.

Photodynamic therapy (PDT), emerging as a minimally invasive therapeutic modality with precise controllability and high spatiotemporal accuracy, has earned significant advancements in the field of cancer and other non-cancerous diseases treatment. Thereinto, type I PDT represents an irreplaceable and meritorious part in contributing to these delightful achievements since its distinctive hypoxia tolerance can perfectly compensate for the high oxygen-dependent type II PDT, particularly in hypoxic tissues. Regarding the diverse type I photosensitizers (PSs) that light up type I PDT, aggregation-induced emission (AIE)-active type I PSs are currently arousing great research interest owing to their distinguished AIE and aggregation-induced generation of reactive oxygen species (AIE-ROS) features. In this review, we offer a comprehensive overview of the cutting-edge advances of novel AIE-active type I PSs by delineating the photophysical and photochemical mechanisms of the type I pathway, summarizing the current molecular design strategies for promoting the type I process, and showcasing current bioapplications, in succession. Notably, the strategies to construct highly efficient type I AIE PSs were elucidated in detail from the two aspects of introducing high electron affinity groups, and enhancing intramolecular charge transfer (ICT) intensity. Lastly, we present a brief conclusion, and a discussion on the current limitations and proposed opportunities.

Photothermal Regulated Nanozyme of CuFeS2 Nanoparticles for Efficiently Promoting Wound Healing Infected by Multidrug Resistant Bacteria.

Peroxidase-mediated chemokinetic therapy (CDT) can effectively resist bacteria; however, factors such as the high dosage of drugs seriously limit the antibacterial effect. Herein, CuFeS2 nanoparticles (NPs) nanozyme antibacterial system with the photothermal effect and peroxidase-like catalytic activity are proposed as a combined antibacterial agent with biosafety, high-efficiency, and broad-spectrum antibacterial ability. In addition, the as-obtained CuFeS2 NPs with a low doses of Cu+ and Fe3+ can change the permeability of bacterial cell membranes and break the antioxidant balance by consuming intracellular glutathione (GSH), which results in more conducive ROS production. Meanwhile, the photothermal heating can regulate the CuFeS2 NPs close to their optimal reaction temperature (60 °C) to release more hydroxyl radical in low concentrations of H2O2 (100 µM). The proposed CuFeS2 NPs-based antibacterial system achieve more than 99% inactivation efficiency of methicillin-resistant Staphylococcus aureus (106 CFU mL-1 MRSA), hyperspectral bacteria ß-Escherichia coli (106 CFU mL-1 ESBL) and Pseudomonas aeruginosa (106 CFU mL-1 PA), even at low concentration (2 µg mL-1), which is superior to those of the conventional CuO NPs at 4 mg mL-1 reported in the literature. In vivo experiments further confirm that CuFeS2 NPs can effectively treat wounds infected by MRSA and promote the wound healing. This study demonstrates that excellent antibacterial ability and good biocompatibility make CuFeS2 NPs a potential anti-infection nanozyme with broad application prospects.

Sono-assisted-thrombolysis by three-dimensional diagnostic ultrasound improves epicardial recanalization and microvascular perfusion in acute myocardial infarction.

Background: This study aimed to evaluate the multiple interactions between therapeutic ultrasound (TUS), microbubbles (MB), and recombinant tissue plasminogen activator (r-tPA) by using three-dimensional (3D) ultrasound to examine the impact of thrombolysis with r-tPA on epicardial recanalization and microcirculation in patients with acute ST-segment-elevation myocardial infarction (STEMI). Methods: Acute thrombotic occlusion of the left anterior descending (LAD) artery was induced in 32 Bama pigs, who were fed a high-cholesterol diet and randomized into four groups: (I) a 3D-sono-assisted-thrombolysis (3D/TUS + MB + r-tPA) group; (II) a 3D/TUS + MB group; (III) a full-dose r-tPA group; and (IV) a 3D/TUS alone group. Epicardial angiographic recanalization rate, microcirculation in the at-risk myocardium, ST-segment elevation on electrocardiogram, and changes in the at-risk myocardium and the myocardial infarct area were compared between the groups. Results: After treatment, distal LAD recanalization was observed in 87.5% (7/8) of pigs in the 3D/TUS + MB + r-tPA group, which was significantly higher than the rates observed in the 3D/TUS + MB (37.5%) and the full-dose r-tPA (50.0%) groups (all P<0.05). The average acoustic intensity in the 3D/TUS + MB + r-tPA group (193.78±10.15 dB) was also significantly higher than that in the 3D/TUS + MB (154.29±31.94 dB) and the r-tPA (141.42±28.31 dB) groups (all P<0.05). The decrease in ST-segment elevation in the 3D/TUS + MB + r-tPA group (1.31±1.22 mm) was significantly higher than that in the 3D/TUS + MB (5.38±1.77 mm) and the r-tPA (4.30±2.08 mm) groups (all P<0.05). Furthermore, the ratio of the infarcted myocardial area divided by the at-risk myocardial area was markedly lower in the 3D/TUS + MB + r-tPA group (0.51±0.14) than in the 3D/TUS + MB (0.69±0.28) and r-tPA (0.75±0.23) groups (all P<0.05). Conclusions: Three-dimensional sono-assisted-thrombolysis directly improves infarct-related recanalization rates, enhances microcirculation, reduces r-tPA dosage, and ameliorates the thrombolytic effect of r-tPA in acute STEMI.

[Study on salt stress tolerance of Chrysanthemum morifolium 'Hangbaiju' and 'Huangju' and F1 seedlings].

OBJECTIVE: To study the salt stress tolerance of Hongxinju, Huangju and F1 seedlings from orthogonal and reciprocal cross under different salt treatments. Grope for transmissibility of salt tolerance between parents and F1 seedlings, and relativity between flavone, chlorogenic acid contents and salt tolerance. METHOD: The materials were put in 5 different concentrations of Hoagland nutrient solution (0, 40, 80, 120, 160 mmol x L(-1)) containing NaCl, keeping grads while raising the consistency of NaCl day by day. The injured leaf area per plant, proline, betaine, MDA, flavones and chlorogenic acid contents were measured and analyzed after treatment. RESULT: As NaCl concentration was below 120 mmol x L(-1), the salt tolerance of Hongxinju was higher than that of Huangju, the salt tolerance of Hongxinju x Huangju higher than that of parents, the salt tolerance of Huangju x Hongxinju was at the level of parents. As NaCl concentration between 120 to 160 mmol x L(-1), the salt tolerance of Huangju was higher than that of Hongxinju, the salt tolerance of Huangju x Hongxinju higher than that of parents and the salt tolerance of Hongxinju x Huangju was at the level of parents. CONCLUSION: Salt tolerance of F1 is more influenced by female parent, relativity showed between flavonoids, chlorogenic acid contents and salt tolerance.

Synergistical Starvation and Chemo-Dynamic Therapy for Combating Multidrug-Resistant Bacteria and Accelerating Diabetic Wound Healing.

The application of the antibiotic drug has dramatically decreased the infection and promoted the development of surgery, but drug-resistant bacteria appeared along with the abuse of antibiotics. Especially, wound in diabetic patients provides more glucose for bacteria resulting in poor wound healing. Therefore, it is imminent to explore advanced agents for combating multidrug-resistant bacteria and accelerating diabetic wound healing. Herein, metal-organic frameworks based nanoreactors loaded with glucose oxidase (GOx) and peroxidase-like bovine hemoglobin (BHb) are designed to construct an effective cascaded catalytic antibacterial system. Therein, GOx can cost the glucose, and release H2 O2 simultaneously, which can then be transformed into hydroxyl radicals by BHb. As a result, the as-prepared nanoreactors can play the roles of both starving and killing toward the multidrug-resistant bacteria. Furthermore, the produced gluconic acid can reduce the pH of working condition, which is beneficial for both the enhancement of peroxidase activity and the inhibition of the bacteria growth. More importantly, the constructed nanoreactors can be degraded and excreted from the body in the form of feces, which render the as-proposed nanoreactors qualified as effective and safe materials for both combating multidrug-resistant bacteria in vitro and accelerating the diabetic wound healing in vivo of the mouse model.

Establishment of anti-oxidation platform based on few-layer molybdenum disulfide nanosheet-coated titanium dioxide nanobelt nanocomposite.

The nanozyme-based antioxidant system could protect normal cells from oxidative stress due to their reactive oxygen species (ROS) scavenging activity and good chemical stability. However, its use is limited for practical in vivo applications due to the high cost and poor biocompatibility (low catalytic efficiency). Herein, MoS2 decorated on TiO2 nanobelts (MoS2@TiO2) was prepared for antioxidation applications. The as-prepared MoS2@TiO2 heterostructure with 50 wt% MoS2 showed the highest efficient catalase activity and superoxide dismutase (SOD) activity under normal physiological conditions. The composite was superior to its single component in terms of enhanced dispersibility and catalytic performance resulting from the higher surface specific area and more exposed active sites. MoS2@TiO2 was not only confirmed to have good in vitro and in vivo biocompatibility but can also effectively eliminate the endogenous excessive accumulation of ROS caused by oxidative stress using the fibroblast cell (L929) line as a model. Further experiments confirmed that in the established mouse oxidative stress model, MoS2@TiO2 can quickly restore the ROS to a normal level in the oxidative stress site of the mouse. These results indicated that MoS2@TiO2 enzyme-like nanomaterials can provide a huge therapeutic potential in future antioxidant defence applications.

Correlations between glycolysis with clinical traits and immune function in bladder urothelial carcinoma.

BACKGROUND: Glycolysis was a representative hallmark in the tumor microenvironment (TME), and we aimed to explore the correlations between glycolysis with immune activity and clinical traits in bladder urothelial carcinoma (BLCA). METHODS: Our study obtained glycolysis scores for each BLCA samples from TCGA by a single-sample gene set enrichment analysis (ssGSEA) algorithm, based on a glycolytic gene set. The relationship between glycolysis with prognosis, clinical characteristics, and immune function were investigated subsequently. RESULTS: We found that enhanced glycolysis was associated with poor prognosis and metastasis in BLCA. Moreover, glycolysis had a close correlation with immune function, and enhanced glycolysis increased immune activities. In other words, glycolysis had a positive correlation with immune activities. Immune checkpoints such as IDO1, CD274, were up-regulated in high-glycolysis group as well. CONCLUSION: We speculated that in BLCA, elevated glycolysis enhanced immune function, which caused tumor cells to overexpress immune checkpoints to evade immune surveillance. Inhibition of glycolysis might be a promising assistant for immunotherapy in bladder cancer.

Response and safety of whole-brain radiotherapy plus temozolomide for patients with brain metastases of non-small-cell lung cancer: A meta-analysis.

OBJECTIVE: The aim of the present work was to investigate the response and safety of whole-brain radiotherapy (WBRT) plus temozolomide (TMZ) for patients with brain metastases of non-small-cell lung cancer (NSCLC). METHODS: The electronic databases of Pubmed, EMbase, Cochrane, Wangfang, china national knowledge infrastructure (CNKI), and Google scholar were systematically searched to identify the prospective randomized trials relevant to WBRT plus TMZ for patients with brain metastases of NSCLC. The data associated with treatment response and toxicity were extracted from original included studies. The relative risk (RR) for treatment response and toxicity between WBRT+TMZ and WBRT alone was pooled by fixed or random effect model. Publication bias was investigated by Begg's funnel plot and Egger's line regression test. RESULTS: Twenty-five clinical trials fulfilled the inclusion criteria and were included in the meta-analysis. The pooled results showed WBRT+TMZ can significant improve the objective response rate (ORR) compared with WBRT alone (RR = 1.43, 95% confidence interval [CI] 1.32-1.55, p < 0.05) under a fixed effect model. WBRT+TMZ significantly increased the III-IV hematological toxicity compared to WBRT alone (RR = 1.66, 95% CI 1.12-2.54, p < 0.05) in the fixed effect model. Grade III-IV gastrointestinal toxicity was increased in WBRT+TMZ compared to WBRT alone (RR = 1.72, 95% CI 1.29-2.30, p < 0.05). Begg's funnel plot and Egger's line regression test indicated publication bias. CONCLUSION: Based on the present work, WBRT+TMZ can improve the ORR for brain metastases of NSCLC, but the risk of treatment-associated grade III/IV hematological toxicity and gastrointestinal toxicity were also increased compared to WBRT alone.

Ultrasound-Mediated Microbubble Cavitation Transiently Reverses Acute Hindlimb Tissue Ischemia through Augmentation of Microcirculation Perfusion via the eNOS/NO Pathway.

Ultrasound-mediated microbubble cavitation improves perfusion in chronic limb and myocardial ischemia. The purpose of this study was to determine the effects of ultrasound-mediated microbubble cavitation in acute limb ischemia and investigate the mechanism of action. The animal with acute hindlimb ischemia was established using male Sprague-Dawley rats. The rats were randomly divided into three groups: intermittent high-mechanical-index ultrasound pulses combined with microbubbles (ultrasound [US] + MB group), US alone (US group) and MB alone (MB group). Both hindlimbs were treated for 10 min. Contrast ultrasound perfusion imaging of both hindlimbs was performed immediately and 5, 10, 15, 20 and 25 min after treatment. The role of the nitric oxide (NO) pathway in increasing blood flow in acutely ischemic tissue was evaluated by inhibiting endothelial nitric oxide synthase (eNOS) with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). In the US + MB group, microvascular blood volume and microvascular blood flow of the ischemic hindlimb were significantly increased after treatment (both p values <0.05), while the microvascular flux rate (ß) increased, but not significantly (p > 0.05). The increases were observed immediately after treatment, and had dissipated by 25 min. Changes in the US and MB groups were minimal. Inhibitory studies indicated cavitation increased phospho-eNOS concentration in ischemic hindlimb muscle tissue, and the increase was significantly inhibited by L-NAME (p < 0.05). Ultrasound-mediated microbubble cavitation transiently increases local perfusion in acutely ischemic tissue, mainly by improving microcirculatory perfusion. The eNOS/NO signaling pathway appears to be an important mediator of the effect.

Establishment and Validation of a Prognostic Risk Model for Autophagy-Related Genes in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Autophagy plays an essential role in tumorigenesis. At present, due to the unclear role of autophagy in renal clear cell carcinoma, we studied the potential value of autophagy-related genes (ARGs) in renal clear cell carcinoma (ccRCC). METHODS: We obtained all ccRCC data from The Cancer Genome Atlas (TCGA). We extracted the expression data of ARGs for difference analysis and carried out biological function analysis on the different results. The autophagy risk model was constructed. The 5-year survival rate was assessed using the model, and the predictive power of the model was evaluated from multiple perspectives. Cox regression analysis was use to assess whether the model could be an independent prognostic factor. Finally, the correlation between the model and clinical indicators is analyzed. RESULTS: The patients were divided into the high-risk group and low-risk group according to the median of autophagy risk score, and the results showed that the prognosis of the low-risk group was better than that of a high-risk group. The validation results of external data sets show that our model has good predictive value for ccRCC patients. The model can be an independent prognostic factor. Finally, the results show that our model has a stable predictive ability. CONCLUSION: The autophagy gene model we constructed can be used as an excellent prognostic indicator for ccRCC. Our study provides the possibility of individualized and precise treatment for ccRCC patients.

Ketamine induces endoplasmic reticulum stress in rats and SV-HUC-1 human uroepithelial cells by activating NLRP3/TXNIP aix.

Many clinical studies have been conducted on ketamine-associated cystitis. However, the underlying mechanisms of ketamine-associated cystitis still remain unclear. Bladder tissues of rats were stained by Hematoxylin and Eosin (HE). The viability of human uroepithelial cells (SV-HUC-1 cells) was determined by cell counting kit-8 (CCK-8). Apoptosis and reactive oxygen species (ROS) were examined by flow cytometry. Additionally, the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß and IL-18 were respectively determined by reverse transcription quantitative (RTq)-PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA and protein levels of B-cell lymphoma/leukemia-2 (Bcl2), Bcl-2-associated X protein (Bax), cleaved caspase 3, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), NOD-like receptor 3 (NLRP3), thioredoxin-interacting protein (TXNIP), Catalase and MnSOD were examined by RT-qPCR and Western blot. Small interfering RNA target TXNIP transfection was performed using Lipofectamine™ 2000. We found that ketamine effectively damaged bladder tissues of rats and promoted apoptosis through regulating the expression levels of GRP78, CHOP, Bcl-2, Bax and cleaved Caspase-3 proteins in vivo and in vitro. NLRP3 inflammatory body and TXNIP were activated by ketamine, which was supported by the changes in TNF-α, IL-6, IL-1 and IL-18 in vivo and in vitro. Furthermore, knocking down TXNIP reversed the effects of ketamine on apoptosis and NLRP3 inflammatory body in SV-HUC-1 cells. Meanwhile, the changes of Catalase and MnSOD showed that ROS was enhanced by ketamine, however, such an effect was ameliorated by down-regulation of TXNIP in SV-HUC-1 cells. Ketamine promoted cell apoptosis and induced inflammation in vivo and in vitro by regulating NLRP3/TXNIP aix.