Melatonin serves as a novel treatment in bladder fibrosis through TGF-ß1/Smad and EMT.

BACKGROUND: Melatonin (MEL) is an indole amine molecule primarily produced in the pineal gland. Melatonin has been shown in numerous studies to have antifibrotic effects on the kidney, liver, and other organs. However, it is still unclear how melatonin works in bladder fibrosis. We explored how melatonin affects animals with bladder fibrosis and the underlying mechanisms. MATERIALS AND METHODS: MEL was used to treat human bladder smooth muscle cells (HBdSMCs) after they were stimulated with transforming growth factor-ß1 (TGF-ß1) in vitro. Proteomic analysis and bioinformatic analysis of the altered expression of these proteins were subsequently performed on HBdSMCs from the different processing methods. To construct an in vivo bladder fibrosis model, we injected protamine sulfate (PS) and lipopolysaccharide (LPS) twice a week into the rat bladder for six weeks. After two weeks of PS/LPS treatment, the mice in the treatment group were treated with MEL (20 mg/kg/d) for 4 weeks. Finally, we detected the expression of fibrosis markers from different perspectives. The TGF-ß1/Smad pathway and epithelial-mesenchymal transition (EMT) in cell and bladder tissues were also identified. Further proteomic analysis was also performed. RESULTS: In vitro, we found that TGF-ß1 treatment enhanced the expression of the fibrosis markers collagen III and α-SMA in HBdSMCs. E-cadherin expression decreased while the TGF-ß1/Smad pathway was activated. Vimentin and N-cadherin expression was also elevated at the same time. Similar findings were observed in the LPS group. After MEL treatment, the expression of collagen III and α-SMA decreased, the expression of E-cadherin increased, and the expression of vimentin and N-cadherin also decreased. According to our quantitative proteomics analysis, CCN1 and SQLE may be important proteins involved in the development of bladder fibrosis. MEL decreased the expression of these genes, leading to the relief of bladder fibrosis. Bioinformatics analysis revealed that the extracellular space structure related to metabolic pathways, actin filament binding, and stress fibers can serve as a pivotal focus in the management of fibrosis. CONCLUSION: Melatonin attenuates bladder fibrosis by blocking the TGF-ß1/Smad pathway and EMT. CCN1 appears to be a possible therapeutic target for bladder fibrosis.

Establishment of colloidal gold immunochromatography strip for rapid detection of Karen mikimotoi and its application.

In China, harmful algal blooms (HABs) are one of the most prominent ecological disasters in the coastal areas. Among the harmful algae species that cause HABs, Karen mikimotoi is a kind of algae that appear frequently. It can secrete hemolytic toxins and fish toxins such as glycolipids and unsaturated fatty, posing a significant threat to marine life. In order to establish a fast and effective detection technology for Karen mikimotoi that can be promoted and applied on site, we have developed a test strip which is based on monoclonal antibody technology and the colloidal gold immune-chromatography assay (GICA). The experimental results show that this test strip can detect different growth stages including growth, and stable and recession period of Karen mikimotoi. The detection results can be displayed within 3-15 min. It had high sensitivity and specificity, with a detection limit of 754 cells/mL. A colorimetric card was made to further determine the concentration of algae detected. What is more, we had developed a method that can be used for on-site enrichment of algae cells using a syringe to detect lower concentrations of Karen mikimotoi, with a minimum detection concentration of 100 cells/mL. Also the test strip was used for on-site testing along the coast of China. This test strip not only serves as a warning for the outbreak of red tide, but also provides a new approach for the development of rapid detection technology for red tide algae.

Near-90° Switch in the Polar Axis of Dion-Jacobson Perovskites by Halide Substitution.

Ferroelectricity in two-dimensional hybrid (2D) organic-inorganic perovskites (HOIPs) can be engineered by tuning the chemical composition of the organic or inorganic components to lower the structural symmetry and order-disorder phase change. Less efforts are made toward understanding how the direction of the polar axis is affected by the chemical structure, which directly impacts the anisotropic charge order and nonlinear optical response. To date, the reported ferroelectric 2D Dion-Jacobson (DJ) [PbI4]2- perovskites exhibit exclusively out-of-plane polarization. Here, we discover that the polar axis in ferroelectric 2D Dion-Jacobson (DJ) perovskites can be tuned from the out-of-plane (OOP) to the in-plane (IP) direction by substituting the iodide with bromide in the lead halide layer. The spatial symmetry of the nonlinear optical response in bromide and iodide DJ perovskites was probed by polarized second harmonic generation (SHG). Density functional theory calculations revealed that the switching of the polar axis, synonymous with the change in the orientation of the sum of the dipole moments (DMs) of organic cations, is caused by the conformation change of organic cations induced by halide substitution.

Catalytic hydrothermal carbonization of wet organic solid waste: A review.

Hydrothermal carbonization has gained attention in converting wet organic solid waste into hydrochar with many applications such as solid fuel, energy storage material precursor, fertilizer or soil conditioner. Recently, various catalysts such as organic and inorganic catalysts are employed to guide the properties of the hydrochar. This review presents a summarize and a critical discussion on types of catalysts, process parameters and catalytic mechanisms. The catalytic impact of carboxylic acids is related to their acidity level and the number of carboxylic groups. The catalysis level with strong mineral acids is likely related to the number of hydronium ions liberated from their hydrolysis. The impact of inorganic salts is determined by the Lewis acidity of the cation. The metallic ions in metallic salts may incorporate into the hydrochar and increase the ash of the hydrochar. The selection of catalysts for various applications of hydrochars and the environmental and the techno-economic aspects of the process are also presented. Although some catalysts might enhance the characteristics of hydrochar for various applications, these catalysts may also result in considerable carbon loss, particularly in the case of organic acid catalysts, which may potentially ruin the overall advantage of the process. Overall, depending on the expected application of the hydrochar, the type of catalyst and the amount of catalyst loading requires careful consideration. Some recommendations are made for future investigations to improve laboratory-scale process comprehension and understanding of pathways as well as to encourage widespread industrial adoption.

Development of a test strip for rapid detection of Gymnodinium catenatum.

Harmful algal blooms (HABs) are major ecological and environmental problems in China's coastal waters and seriously threaten the stability of the marine ecosystem and human health. Gymnodinium catenatum is a toxic red tide dinoflagellate. It can produce paralytic shellfish toxins (PSP), which cause serious hazards to marine organisms, public health, and safety. In this paper, a test strip based on colloidal gold immunochromatography (GICG) was developed for the rapid detection of Gymnodinium catenatum. The experimental results showed that the test strip has good specificity and sensitivity. It not only detects the different components of Gymnodinium catenatum but also may detect algal toxins. The lowest density of Gymnodinium catenatum that can be detected by this test strip is approximately 120 cells/mL. Cross-reaction indicated that the test strip had a high specificity for Gymnodinium catenatum. This test strip provides a rapid method for in situ detection of Gymnodinium catenatum and a reference method for the monitoring of other harmful algae to serve as an early warning of upcoming red tides. It also provides a new way to prepare more detection methods for toxic algal toxins.

Effect of Transcatheter Arterial Chemoembolization Combined with Radiofrequency Ablation on Liver Function and Immune Function in Patients with Hepatocellular Carcinoma.

Objectives: To investigate the effects of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) on liver function and immune function in patients with hepatocellular carcinoma (HCC). Methods: From December 2016 to January 2019, patients with primary liver cancer who could not be operated on were selected as the study subjects. 170 patients were randomly divided into two groups. The control group was treated with transcatheter arterial chemoembolization (n = 85). The patients in the observation group were treated with transcatheter arterial chemoembolization combined with radiofrequency ablation (n = 85). The clinical effects of the two groups were analyzed. The changes of liver function and immune function were detected by automatic biochemical analyzer before and after treatment. The changes of hypoxia inducible factor-1 (HIF1) alpha and vascular endothelial growth factor (VEGF) levels before and after treatment were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: The total effective rate in the observation group was significantly higher than that in the control group (P < 0.05). After treatment, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), CD8+, HIF1 alpha, and VEGF decreased significantly (P < 0.05), while levels of total bilirubin, direct bilirubin, indirect bilirubin, CD3+, CD4+, and CD4+/CD8+ increased significantly (P < 0.05). The changes of the above indexes in the observation group were more significant than those in the control group (P < 0.05). Conclusion: Hepatic arterial chemoembolization combined with radiofrequency ablation has a significant effect on liver function and immune function in patients with liver cancer, which may be related to the abnormal levels of HIF1α and vascular endothelial growth factor.

Cytokine storm: behind the scenes of the collateral circulation after acute myocardial infarction.

At least 17 million people die from acute myocardial infarction (AMI) every year, ranking it first among causes of death of human beings, and its incidence is gradually increasing. Typical characteristics of AMI include acute onset and poor prognosis. At present, there is no satisfactory treatment, but development of coronary collateral circulation (CCC) can be key to improving prognosis. Recent research indicates that the levels of cytokines, including those related to promoting inflammatory responses and angiogenesis, increase after the onset of AMI. In the early phase of AMI, cytokines play a vital role in inducing development of collateral circulation. However, when myocardial infarction is decompensated, cytokine secretion increases greatly, which may induce a cytokine storm and worsen prognosis. Cytokines can regulate the activation of a variety of signal pathways and form a complex network, which may promote or inhibit the establishment of collateral circulation. We searched for published articles in PubMed and Google Scholar, employing the keyword "acute myocardial infarction", "coronary collateral circulation" and "cytokine storm", to clarify the relationship between AMI and a cytokine storm, and how a cytokine storm affects the growth of collateral circulation after AMI, so as to explore treatment methods based on cytokine agents or inhibitors used to improve prognosis of AMI.

Potential Pathophysiological Mechanisms Underlying Multiple Organ Dysfunction in Cytokine Release Syndrome.

In recent decades, many serious respiratory infections have broken out all over the world, including SARS-CoV, MERS, and COVID-19. They are characterized by strong infectivity, rapid disease progression, high mortality, and poor prognosis. Excessive immune system activation results in cytokine hypersecretion, which is an important reason for the aggravation of symptoms, and can spread throughout the body leading to systemic multiple organ dysfunction, namely, cytokine release syndrome (CRS). Although many diseases related to CRS have been identified, the mechanism of CRS is rarely mentioned clearly. This review is intended to clarify the pathogenetic mechanism of CRS in the deterioration of related diseases, describe the important signaling pathways and clinical pathophysiological characteristics of CRS, and provide ideas for further research and development of specific drugs for corresponding targets to treat CRS.

mRNA vaccine-a desirable therapeutic strategy for surmounting COVID-19 pandemic.

As an acute respiratory infectious disease, COVID-19 threatens the safety of global public health. Given the current lack of specific treatment against this disease, research and development of vaccines have become sharp weapons for overcoming the pandemic. mRNA vaccines have become the lead in COVID-19 vaccination strategies due to their advantages, such as rapid industrial production and efficacy. A total of 137 COVID-19 vaccines have entered the clinical trial stage, among which 23 are mRNA vaccines, accounting for 17% of the total vaccines. Herein, we summarize the research and developmental processes of mRNA vaccines as well as the approach for protecting the human body against infection. Focusing on the latest clinical trial data of two COVID-19 mRNA vaccines from Pfizer and Modena, we discuss their effectiveness and safety. Finally, we analyze the challenges and problems that mRNA vaccines face in controlling the COVID-19 pandemic.

Diagnostic and prognostic value of serum Chitinase 3-like protein 1 in hepatocellular carcinoma.

The serum Chitinase 3-like protein 1 (CHI3L1) protein level can distinguish the stages of liver fibrosis to a great extent. However, the diagnostic and prognostic significance of serum CHI3L1 in hepatocellular carcinoma (HCC) is not clarified. To evaluate the diagnostic and prognostic value of CHI3L1 in HCC, a total of 128 HCC patients treated in the HwaMei Hospital, University of Chinese Academy of Sciences, from December 2018 to April 2020 were collected retrospectively. Matched age and gender subjects, 40 patients with liver cirrhosis, 40 patients with chronic hepatitis, and 40 healthy subjects were enrolled in the control group. The relevant clinical laboratory and examination data and the overall survival time (OS) of the HCC patients were collected. The serum CHI3L1 expression level is related to α-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, maximum tumor diameter, liver cirrhosis, and HCC patient's OS (p < 0.05). The area under the curve (AUC) of CHI3L1 was 0.7875 with the cutoff value of 91.36 ng/ml. Combining the serum CHI3L1 and α-fetoprotein (AFP) by a binary logistic regression model can increase the diagnostic sensitivity to 97.5%. Multivariate Cox regression analysis indicated that CHI3L1 is an independent prognostic factor in patients with HCC.

Direct Detection and Visualization of the H+ Reaction Process in a VO2 Cathode for Aqueous Zinc-Ion Batteries.

Because they are safer and less costly than state-of-the-art Li-ion batteries, aqueous zinc-ion batteries (AZIBs) have been attracting more attention in stationary energy storage and industrial energy storage. However, the electrochemical reaction of H+ in all of the cathode materials of AZIBs has been puzzling until now. Herein, highly oriented VO2 monocrystals grown on a Ti current collector (VO2-Ti) were rationally designed as the research model, and such a well-aligned VO2 cathode also displayed excellent zinc-ion storage capability (e.g., a reversible capacity of 148.4 mAh/g at a current density of 2 A/g). To visualize the H+ reaction process, we used time-of-flight secondary-ion mass spectrometry. With the benefit of such a binder-free and conductor-free electrode design, a clear and intuitive reaction of H+ in a VO2 cathode is obtained, which is quite significant for unraveling the accurate reaction mechanism of VO2 in AZIBs.

High-Density Reconfigurable Synaptic Transistors Targeting a Minimalist Neural Network.

Enormous synaptic devices are required to build a parallel, precise, and efficient neural computing system. To further improve the energy efficiency of neuromorphic computing, a single high-density synaptic (HDS) device with multiple nonvolatile synaptic states is suggested to reduce the number of synaptic devices in the neural network, although such a powerful synaptic device is rarely demonstrated. Here, a photoisomerism material, namely, diarylethene, whose energy level varies with the wavelength of illumination is first introduced to construct a powerful HDS device. The multiple synaptic states of the HDS device are intrinsically converted under UV-vis regulation and remain nonvolatile after the removal of illumination. More importantly, the conversion is reconfigurable and reversible under different light conditions, and the synaptic characteristics are comprehensively mimicked in each state. Finally, compared with a two-layer multilayer perceptron (MLP) architecture based on static synaptic devices, the HDS device-based architecture reduces the device number by 16 times to achieve a minimalist neural computing structure. The invention of the HDS device opens up a revolutionary paradigm for the establishment of a brain-like network.

Electret-Based Organic Synaptic Transistor for Neuromorphic Computing.

Neuromorphic computing inspired by the neural systems in human brain will overcome the issue of independent information processing and storage. An artificial synaptic device as a basic unit of a neuromorphic computing system can perform signal processing with low power consumption, and exploring different types of synaptic transistors is essential to provide suitable artificial synaptic devices for artificial intelligence. Hence, for the first time, an electret-based synaptic transistor (EST) is presented, which successfully shows synaptic behaviors including excitatory/inhibitory postsynaptic current, paired-pulse facilitation/depression, long-term memory, and high-pass filtering. Moreover, a neuromorphic computing simulation based on our EST is performed using the handwritten artificial neural network, which exhibits an excellent recognition accuracy (85.88%) after 120 learning epochs, higher than most reported organic synaptic transistors and close to the ideal accuracy (92.11%). Such a novel synaptic device enriches the diversity of synaptic transistors, laying the foundation for the diversified development of the next generation of neuromorphic computing systems.

Drinking water: a risk factor for high incidence of esophageal cancer in Anyang, China.

Anyang is known to be a high-incidence area of esophageal cancer (EC) in China. Among a long list of risk factors, the quality of drinking water was evaluated. We have selected 3806 individuals and collected 550 drinking water samples correspondent with this not-matched case-control survey. There are 531 EC patients included based on Population Cancer Registry from 92 townships, of which 3275 controls with long-lived aged over 90 years and free from EC are used as controls in the same regions. Our result suggests that the quality of drinking water is a highly associated risk factor for EC. The residential ecological environment and the quality of water resource positively link with each other. The analysis of water samples also demonstrated that the concentrations of methyl ethylamine, morpholine, N-methylbenzylamine, nitrate and chloride in water from springs and rivers are higher than those in well and tap water (P = 0.001). Micronuclei formation tests show that well water and tap water in these regions have no mutagenicity.

[Autologous transplantation of bone marrow stem cells versus peripheral blood stem cells for treatment of decompensate liver cirrhosis: a comparative study of 30 cases].

Not Abstract.

Detection Of QRS-Wave In Electrocardiogram: Based On Kalman And Wavelets.

An algorithm using wavelets and Kalman filtering method has been developed for QRS detection. The algorithm takes following steps: i) We use a RLS adaptive algorithm to establish a model of the electrocardiogram. Thus the algorithm can change its own model according to the change of the electrocardiogram. ii) Based on the model established in stage i), we combined the wavelet and Kalman Algorithm, decomposed the signal to several scales, filtering the signal in each scale. And then, iii)A decision rule is used to determine the QRS complex. The method was tested on ECG data form the MIT database, and experimental results show that the method is effective, and the influence of the noise can be eliminated.