Establishment of an immortalized cell line derived from human adenomyosis ectopic lesions.

Because adenomyosis (AM) ectopic primary cells are hard to come by, have a short lifespan, and the characteristics that alter over time, their utility in AM research is constrained. This study aimed to establish a line of immortalized human adenomyosis ectopic cell (ihAMEC) to change this situation. Primary cells were obtained from AM ectopic lesion tissue and then infected with Simian Vacuolating Virus 40 Tag (SV40 T) lentivirus and screened to establish immortalized cells. We verified the main features and found that the ihAMEC could be cultured for more than 50 generations and the proliferation ability of ihAMEC was more active than that of primary cells. The cytoskeleton and cell types of ihAMEC were similar to primary cells and maintained a normal karyotype. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins, and estrogen/progesterone receptors in ihAMEC was similar to the expression seen in primary cells. In addition, the response of ihAMEC under estrogen treatment and Lipopolysaccharide intervention is similar to primary cells. The clonogenic ability of ihAMEC was lower than tumor cells and did not form tumors in tumorigenicity assays. Thus, ihAMEC can be used as in vitro cellular model for pathogenesis and drug development studies regarding AM.

How inflammation dictates diabetic peripheral neuropathy: An enlightening review.

BACKGROUND: Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN. AIMS: This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response. METHODS: We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed. RESULTS: In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes. CONCLUSIONS: This review is distinguished by synthesizing cutting-edge mechanisms linking inflammation to DPN and identifying innovative, inflammation-targeted therapeutic approaches.

How vitamins act as novel agents for ameliorating diabetic peripheral neuropathy: A comprehensive overview.

Diabetic peripheral neuropathy (DPN) is a pervasive and incapacitating sequela of diabetes, affecting a significant proportion of those diagnosed with the disease, yet an effective treatment remains elusive. Vitamins have been extensively studied, emerging as a promising target for diagnosing and treating various systemic diseases, but their role in DPN is not known. This review collates and synthesizes knowledge regarding the interplay between vitamins and DPN, drawing on bibliographies from prior studies and relevant articles, and stratifying the therapeutic strategies from prophylactic to interventional. In addition, the clinical evidence supporting the use of vitamins to ameliorate DPN is also evaluated, underscoring the potential of vitamins as putative therapeutic agents. We anticipate that this review will offer novel insights for developing and applying vitamin-based therapies for DPN.

What Is the Impact of the Novel Coronavirus and the Vaccination on Guillain-Barre Syndrome?

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has resulted in devastating medical and economic consequences worldwide over the past 3 years. As the pandemic enters a new stage, it is essential to consider the potential impact on rare diseases such as Guillain-Barre syndrome (GBS), which has been intimately associated with COVID-19 since the first COVID-19-related GBS case was reported in January 2020. There are notable differences between COVID-19-related GBS and GBS without COVID-19 in terms of diagnostic types and clinical manifestations. Furthermore, with the widespread administration of COVID-19 vaccines, there have been reports of GBS occurring shortly after vaccination, which requires close attention despite its rarity. This review also explores the vaccines associated with heightened GBS risks, offering insights that may guide vaccination policies and clinical practice. To provide a visual summary of these findings, we have included a graphical abstract. This article will discuss the characteristic manifestations of GBS patients after being positive for the novel coronavirus and the safety of several COVID-19 vaccines. Firstly, this article comprehensively expounds and discusses the epidemiological aspects of novel coronavirus-related GBS. For example, from the perspective of the same population, the expected incidence of GBS in the COVID-19-positive population (persons/100,000 persons/ year) is about 43 times that of the COVID-19-negative population, and the incidence of GBS is significantly increased. Secondly, the clinical characteristics of COVID-19-negative GBS patients and SARS-CoV-2-GBS (SC2-GBS) patients were summarized and compared. Thirdly, this article reviews GBS cases in the current adverse events after COVID-19 vaccination and analyzes and discusses from multiple perspectives, such as the incidence of GBS events, the age proportion of patients, and the interval of onset.

Exogenous H2S alleviates senescence of glomerular mesangial cells through up-regulating mitophagy by activation of AMPK-ULK1-PINK1-parkin pathway in mice.

Hydrogen sulfide (H2S) is the third gas signaling molecule that has been shown to be involved in the regulating vital activities in the body, including inhibition of aging. However, it is unknown whether H2S alleviates aging in the kidney and glomerular mesangial cells (GMCs) by modulating their mitophagy. Here, results of experiments in vivo and in vitro showed that compared with control group, the renal function of mice and GMCs viability were decreased in D-gal (D-galactose) group, while the activity of SA-ß-gal and p21 expression were increased, Cyclin D1 and Klotho expressions were decreased; H2S content and CSE expression were lower; ROS and MDA contents and mitochondrial permeability transition pore (mPTP) opening were risedose; ATP production and mitochondrial membrane potential (Δψm) were reduced; Apoptotic rate, the expression of Cleaved caspase-9 and -3, Cyt c, p62 and Drp1 were enhanced and the expression of Bcl-2, Mfn2, Beclin-1, LC3 II/I, PINK1 and parkin were decreased. In addition, phospho-AMPK/AMPK and phospho-ULK1/ULK1 were also decreased significantly. Compared with the D-gal group, the changes of above indexes were reversed in the D-gal + NaHS (Sodium hydrosulfide, an exogenous H2S donor) group. The reverse effects of NaHS were similar to that of AICAR (an AMPK agonist) and kinetin (a PINK1 agonist), respectively. Taken together, these results suggest that exogenous H2S increases mitophagy and inhibits apoptosis as well as oxidative stress through up-regulation of AMPK-ULK1-PINK1-parkin pathway, which delays kidney senescence in mice.

Vitamin D and diabetic peripheral neuropathy: A multi-centre nerve conduction study among Chinese patients with type 2 diabetes.

AIMS: Increasing numbers of reports link vitamin D deficiency to diabetic peripheral neuropathy (DPN), yet evidence regarding neurological deficits and electromyogram is scarce. The present multi-centre study sought to investigate these associations based on objective quantifications. MATERIALS AND METHODS: Information on DPN-related symptoms, signs, all diabetic microvascular complications, and nerve conduction abilities (quantified by nerve conduction amplitude and velocity, F-wave minimum latency (FML) of peripheral nerves) were collected from a derivation cohort of 1192 patients with type 2 diabetes (T2D). Correlation, regression analysis, and restricted cubic splines (RCS) were used to explore linear and non-linear relationships between vitamin D and DPN, which were validated in an external cohort of 223 patients. RESULTS: Patients with DPN showed lower levels of vitamin D than those without DPN; patients with vitamin D deficiency (<30 nmol/L) tended to suffer more DPN-related neurological deficits (paraesthesia, prickling, abnormal temperature, ankle hyporeflexia, and distal pall hypoesthesia correlating with MNSI-exam score (Y = -0.005306X + 2.105, P = 0.048). Worse nerve conduction abilities (decreased motor nerve amplitude, sensory nerve amplitude, motor nerve velocity, and increased FML) were also observed in these patients. Vitamin D had a significant threshold association with DPN (adjusted OR = 4.136, P = 0.003; RCS P for non-linearity = 0.003) and correlates with other microvascular complications (diabetic retinopathy and diabetic nephropathy). CONCLUSIONS: Vitamin D is associated with the conduction ability of peripheral nerves and may have a nerve- and threshold-selective relationship with the prevalence and severity of DPN among patients with T2D.

Oxidative Stress in Diabetic Peripheral Neuropathy: Pathway and Mechanism-Based Treatment.

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus with a high incidence. Oxidative stress, which is a crucial pathophysiological pathway of DPN, has attracted much attention. The distortion in the redox balance due to the overproduction of reactive oxygen species (ROS) and the deregulation of antioxidant defense systems promotes oxidative damage in DPN. Therefore, we have focused on the role of oxidative stress in the pathogenesis of DPN and elucidated its interaction with other physiological pathways, such as the glycolytic pathway, polyol pathway, advanced glycosylation end products, protein kinase C pathway, inflammation, and non-coding RNAs. These interactions provide novel therapeutic options targeting oxidative stress for DPN. Furthermore, our review addresses the latest therapeutic strategies targeting oxidative stress for the rehabilitation of DPN. Antioxidant supplements and exercise have been proposed as fundamental therapeutic strategies for diabetic patients through ROS-mediated mechanisms. In addition, several novel drug delivery systems can improve the bioavailability of antioxidants and the efficacy of DPN.

"Green" Extraction and On-Site Rapid Detection of Aflatoxin B1, Zearalenone and Deoxynivalenol in Corn, Rice and Peanut.

The common mycotoxins in polluted grains are aflatoxin B1(AFB1), zearalenone (ZEN) and deoxynivalenol (DON). Because of the potential threat to humans and animals, it is necessary to detect mycotoxin contaminants rapidly. At present, later flow immunoassay (LFIA) is one of the most frequently used methods for rapid analysis. However, multistep sample pretreatment processes and organic solvents are also required to extract mycotoxins from grains. In this study, we developed a one-step and "green" sample pretreatment method without using organic solvents. By combining with LFIA test strips and a handheld detection device, an on-site method for the rapid detection of AFB1, ZEN and DON was developed. The LODs for AFB1, ZEN and DON in corn are 0.90 µg/kg, 7.11 µg/kg and 10.6 µg/kg, respectively, and the working ranges are from 1.25 µg/kg to 40 µg/kg, 20 µg/kg to 2000 µg/kg and 35 µg/kg to 1500 µg/kg, respectively. This method has been successfully applied to the detection of AFB1, ZEN and DON in corn, rice and peanut, with recoveries of 89 ± 3%-106 ± 3%, 86 ± 2%-108 ± 7% and 90 ± 2%-106 ± 10%, respectively. The detection results for the AFB1, ZEN and DON residues in certified reference materials by this method were in good agreement with their certificate values.

Study on the Occurrence Difference of Functional Groups in Coals with Different Metamorphic Degrees.

In order to quantitatively study the difference in occurrence content of functional groups in coals with different metamorphic degrees, the samples of long flame coal, coking coal, and anthracite of three different coal ranks were characterized by FTIR and the relative content of various functional groups in different coal ranks was obtained. The semi-quantitative structural parameters were calculated, and the evolution law of the chemical structure of the coal body was given. The results show that with the increase in the metamorphic degree, the substitution degree of hydrogen atoms on the benzene ring in the aromatic group increases with the increase in the vitrinite reflectance. With the increase in coal rank, the content of phenolic hydroxyl, carboxyl, carbonyl, and other active oxygen-containing groups gradually decreased, and the content of ether bonds gradually increased. Methyl content increased rapidly first and then increased slowly, methylene content increased slowly first and then decreased rapidly, and methylene content decreased first and then increased. With the increase in vitrinite reflectance, the OH-π hydrogen bond gradually increases, the content of hydroxyl self-association hydrogen bond first increases and then decreases, the oxygen-hydrogen bond of hydroxyl ether gradually increases, and the ring hydrogen bond first significantly decreases and then slowly increases. The content of the OH-N hydrogen bond is in direct proportion to the content of nitrogen in coal molecules. It can be seen from the semi-quantitative structural parameters that with the increase in coal rank, the aromatic carbon ratio fa, aromatic degree AR and condensation degree DOC increase gradually. With the increase in coal rank, A(CH2)/A(CH3) first decreases and then increases, hydrocarbon generation potential 'A' first increases and then decreases, maturity 'C' first decreases rapidly and then decreases slowly, and factor D gradually decreases. This paper is valuable for analyzing the occurrence form of functional groups in different coal ranks and clarifying the evolution process of structure in China.

Study on smoke blocking and thermal radiation attenuation by water curtain in tunnel fire.

A 1:10 scale model tunnel with a length, height and width of 9 m, 0.6 m and 0.8 m, respectively, was set up in this paper. A water curtain system was installed in the model to investigate the effect of water curtain systems on smoke flow and heat propagation. A reduced-scale experimental and theoretical study was carried out by varying the heat release rate of the fire source, the water curtain pressure, and the number of water curtain rows. A series of tests were carried out for various setups to quantify each mechanism of interaction between the water mist and hot smoke, to propose a method for qualitatively analysing water curtain systems blocking the propagation of heat radiation and the flow of smoke from combustion, and to propose a method for predicting heat fluxes. The study found that the pressure of the water curtain, the number of rows, and the heat release rate of the fire source all had an effect on the smoke blocking effect of the water curtain system. This effect decreased as the heat release rate of the fire source increased and increased significantly with the pressure of the water curtain and the number of rows. The smoke blocking effect was quantified using conservation of momentum by establishing a dimensionless parameter R to represent the ratio of water curtain momentum to smoke momentum, as well as the ratio of heat flux before and after the water curtain to represent the smoke blocking capacity [Formula: see text] of the water curtain. The smoke blockage rate [Formula: see text] ranges between 40 and 75%, and the smoke blockage rate increases as the momentum R increases. Finally, in tunnel fires, a predictive model for the attenuation of heat radiation by water curtains has been developed, providing theoretical support for the quantitative study of the smoke and thermal blockage effects of water curtains, which is beneficial to the protection of human life in confined spaces.

Simulation of Large-Scale Tunnel Belt Fire and Smoke Characteristics under a Water Curtain System Based on CFD.

Transport belt fires pose a serious threat to the lives of miners. The smoke spread characteristics of transport belt fires are important for the effective construction of underground safety works. In this paper, a water curtain system is added to ventilation to investigate the effectiveness of water spray in blocking fire-induced smoke and heat. Using computational fluid dynamics (CFD) simulations obtained with FDS 6.0.1, full-scale underground belt transport tunnel fire tests are conducted with mechanical ventilation and a water curtain system to obtain smoke spread characteristics, temperature distribution, visibility profiles, and CO distribution. The results show that the addition of a water curtain system can effectively limit temperature and smoke, but high mechanical ventilation velocities are not conducive to the water curtain system, limiting underground tunnel fires. This study found that the mechanical ventilation velocity should be controlled at approximately 0.8 m/s when the water curtain system is on a 100 m beltway. Smoke across the water curtain system area, smoke stratification in the lower layer of the water curtain area is lost, the water curtain system in the lower layer of the tunnel will affect the flow field and temperature field flowing to the fire source, and the blockage effect is the most obvious in the upper layer of the tunnel. The water curtain system reduces the distribution of temperature and CO concentration in the tunnel and rapidly restores visibility. With the addition of the water curtain system, the environment in the restricted area is suitable for occupant evacuation and firefighting, and the system can be considered a viable strategy for tunnel smoke control.

Neutrophil-to-Lymphocyte ratio on admission predicts gastrointestinal bleeding in acute basal ganglia hemorrhage.

BACKGROUND: Gastrointestinal bleeding (GIB) is a potential contributing factor for poor prognosis of spontaneous basal ganglia hemorrhage (BGH). This study aimed to investigate the predictive value of new inflammatory biomarkers including neutrophil to lymphocytes (NLR) on admission and construct a nomogram for rapidly predicting GIB in acute BGH. METHODS: The retrospective study included all patients with acute BGH admitted from the emergency department in Huashan Hospital from July 2017 to January 2019. Multivariate analysis was conducted to evaluate the correlation between factors within 24 h and the occurrence of GIB within 7 days after BGH. The receiver operating characteristic (ROC) curve was performed to estimate the prediction ability of inflammatory biomarkers. A nomogram based on significant predictors was validated by ROC curve and calibration curve. RESULTS: A total of 122 patients were enrolled in this study, and the incidence of GIB was 23.0%. Patients with GIB had larger hematoma volume (≥30 ml), lower Glasgow Coma Scale (GCS) score (≤8) and increased inflammatory biomarkers on admission. ROC curve revealed that NLR had a high predictive value to the complication (area under the curve = 0.87). According to multivariate analysis, NLR, GCS score, and hematoma volume were main factors for nomogram, with good calibration and discrimination. CONCLUSIONS: Neutrophil-to-lymphocyte ratio and GCS score within 24 h after the onset of acute BGH are the independent risk factors for GIB. The nomogram developed by these predictors may assist surgeons in rapidly assessing and preventing of GIB for BGH patients in earlier stage.

Molecular structure characterization analysis and molecular model construction of anthracite.

Coal is the largest non-renewable energy as well as an important basic energy and industrial raw material. Thus, correctly understanding the molecular structure characteristics of coal has important theoretical value for realizing carbon neutralization. In this work, we clarified the molecular structure characteristics of anthracite, where the organic matter in anthracite was characterized and analyzed by industrial/elemental analysis, FTIR, XPS, XRD and solid 13C NMR. The ratio of bridge carbon to the perimeter carbon of anthracite was 0.38, and the degree of condensation in the aromatic structure was high. Nitrogen in coal primarily exists in the form of pyridine and pyrrole. Based on the information on functional group composition, the carbon skeleton structure, and surface element composition, a molecular structure model of Yangquan anthracite could be constructed, where the molecular formula was C208H162O12N4. This study may serve as a reference for researchers in this field to consult and refer to the construction ideas and methods of molecular structure models of different coal samples.

A biomimetic adhesive with high adhesion strength and toughness comprising soybean meal, chitosan, and condensed tannin-functionalized boron nitride nanosheets.

Soybean meal (SM)-based adhesive can solve the issues of formaldehyde emission and over-reliance of aldehyde-based resins but suffers from poor water resistance, weak adhesion strength, and high brittleness. Herein, a high-performance adhesive inspired by lobster cuticular sclerotization was developed using catechol-rich condensed tannin-functionalized boron nitride nanosheets (CT@BNNSs), amino-containing chitosan (CS), and SM (CT@BNNSs/CS/SM). The oxidative crosslinking between the catechol and amino, initiated by oxygen at high temperatures, formed a strengthened and water-resistant interior network. These strong intermolecular interactions induced by phenol-amine synergy accompanied by the reinforcement of uniformly dispersed BNNSs improved the load transfer and energy dissipation capacity, endowing the adhesive with great cohesion strength. Given these synergistic effects, the biomimetic CT@BNNSs/CS/SM adhesive caused noticeable improvements in water tolerance, mechanical strength, and toughness over the neat SM adhesive, e.g., enhanced wet shear strength (1.46 vs. 0.66 MPa, respectively), boiling water shear strength (0.92 vs. 0.43 MPa, respectively), and debonding work (0.368 vs. 0.113 J, respectively). Thus, this study provided a green and low-cost bionic strategy for the preparation of high-performance biomass adhesives.

Production and Selection of Antibody-Antigen Pairs for the Development of Immunoenzyme Assay and Lateral Flow Immunoassay Methods for Carbofuran and Its Analogues.

To produce a sensitive monoclonal antibody (mAb) for the simultaneous detection of carbofuran, benfuracarb, carbosulfan and 3-hydroxy-carbofuran, 2,3-dihydro-2,2-dimethyl-7-benzofuranmethanamine (DDB) was conjugated to bovine serum albumin (BSA) to prepare the immunogen DDB-BSA and mice were immunized. Coating antigens were prepared by conjugating DDB and 5-methoxy-2,3-dihydrobenzofuran-3-acetic acid (MDA) to BSA and ovalbumin (OVA), respectively. Furthermore, the effect of different antibody-antigen pairs on the sensitivity of ELISA and LFIA methods for the detection of carbofuran was investigated. After the immunization, a high-affinity mAb 13C8 was obtained. The ability of the coating antigen to compete with carbofuran for binding antibodies was found to be significantly different between ELISA and LFIA methods. With the antibody-antigen pair 13C8-MDA-OVA, the IC50 values of the ELISA and QD-LFIA methods for carbofuran were 0.18 ng/mL and 0.67 ng/mL, respectively. The cross-reactivity (CR) values of the two methods for benfuracarb, carbosulfan and 3-hydroxy-carbofuran ranged from 72.0% to 83.7%, while, for other carbamate pesticides, the CR values were less than 1%. The spiked recoveries of carbofuran in vegetables by the QD-LFIA method were 83-111%, with a coefficient of variation below 10%, and the test results of the actual samples were consistent with the HPLC-MS method. Overall, this study provides key materials for the development of immunoassays for carbofuran and its analogues, and the antibody-antigen pair selection strategy established in this study provides useful insights for the development of sensitive immunoassays for other compounds.

Deformation Modeling and Simulation of a Novel Bionic Software Robotics Gripping Terminal Driven by Negative Pressure Based on Classical Differential Algorithm.

A general pneumatic soft gripper is proposed in this paper. Combined with the torque balance theory, the mathematical theoretical model of bending deformation of soft gripper is established based on Yeoh constitutive model and classical differential geometry. Assuming that the pressure in each inner cavity is evenly distributed, the input gas is in an ideal state, which is approximately treated as an isothermal condition, and all orifices experience blocked flow. In addition, compared with the mechanical work of gas, the energy related to gas flow and heat transfer is negligible. The nonlinear mechanical properties of silicone rubber are studied. It is regarded as isotropic and incompressible material, which is characterized by strain energy per unit volume. The material constant coefficients C 10 and C 20 are determined through the uniaxial tensile test, and the software gripper is simulated on the ABAQUS platform. The bending deformation models of grippers with three different force-bearing cavity structures are analyzed and compared, and the software clamping structure with the bending deformation most in line with the application conditions is selected. The limit input air pressure of the gripper and the situation of enveloping the clamping target object are analyzed. Through the bending deformation experiment, the maximum deformation angle is 72.4°. The relative error between the simulation analysis data and the prediction results of the mathematical model is no more than 3.5%, which verifies the effectiveness of the simulation and the correctness of the mathematical theoretical model of bending deformation. The soft manipulator proposed in this paper has good adaptability to grasping objects of different shapes and sizes. The minimum diameter of the target object that can be clamped is 0.1 mm. It can clamp the object weighing up to 1 kg. It has compact size, light weight, high ductility, and flexibility.

Study on parameter optimization of deep hole cumulative blasting in low permeability coal seams.

Coal seam gas extraction is an important means of exploiting and utilizing gas resources, as well as a means of preventing coal mine disasters. To improve gas extraction efficiency in high gas and low permeability coal seams while ensuring blasting security, deep hole cumulative blasting parameters were optimized. ANSYS/LS-DYNA software is used to establish a 3-dimensional cumulative blasting model. By comparing and analyzing the blasting stress nephograms, stress time-history curves, and crack expansion curves, the optimal blasthole diameter, charge position, and charge length are obtained. Based on the numerical simulation results, a field test was carried out in the No. 10 coal seam of the Pingdingshan coal mine. The test results show that after cumulative blasting, the gas concentration was increased by an average of 2.25 times, the gas purity was increased by an average of 3.78 times, the permeability coefficient of the coal seam was increased by 21 times, and the effective radius of blasting was up to 7 m. The positive effects of deep hole cumulative blasting parameter optimization on the pressure relief and permeability enhancement of a high gas and low permeability coal seam were determined, which can provide a reference for other similar working faces to implement this technology.

Discovery of aminothiazole derivatives as novel human enterovirus A71 capsid protein inhibitors.

Enterovirus A71 (EV-A71), one of the major pathogens that causes hand, foot and mouth disease (HFMD), has seriously threatened the health and safety of young children. In this study, aminothiazole derivatives were synthesized and screened against EV-A71 in Rhabdomyosarcoma (RD) cells. The best compound (12s), with a biphenyl group, showed activity against EV-A71 (EC50: 0.27 µM) but also against a series of different human enteroviruses without significant cytotoxicity (CC50 > 56.2 µM). Mechanistic studies including time-of-drug-addition assays, viral entry assays and microscale thermophoresis (MST) experiments, showed that 12s binds to EV-A71 capsid and blocks the binding between the viral protein VP1 and the relevant human scavenger receptor class B member 2 (hSCARB2).

BODIPY-NBD dyad for highly selective and sensitive detection of hydrogen sulfide in cells and zebrafish.

Hydrogen sulfide (H2S) has been regarded as the third endogenous gas signaling molecule. The development of suitable tools for H2S detection in vitro and in vivo has always been a focus of research. In this work, three BODIPY-NBD dyads (o/m/p-BNP) were designed and synthesized using BODIPY and NBD as the fluorophore and quencher, respectively. The position of the NBD moiety in the probe showed different fluorescence quenching abilities. All probes showed highly selective to H2S. Probe o-BNP displayed the maximum fluorescence enhancement (c.a. 1300-fold) and the lowest detection limit (105 nM). Probe o-BNP can visualize the production of endogenous H2S in HeLa cells and zebrafish.

Identification of a novel binding inhibitor that blocks the interaction between hSCARB2 and VP1 of enterovirus 71.

Enterovirus 71 (EV-A71) infection causes severe hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children under 5 years of age. Although there are available vaccines for EV-A71 C4, however, there are no efficient drugs for severe cases. Thus, there is an urgent need to find new direct-antiviral agents (DAAs) to control EV-A71 infection. In this study, we report our discovery of the EV-A71 capsid inhibitor PTC-209HBr, a small-molecule Bmi-1 inhibitor and an anticancer agent, and its derivatives that inhibit multiple enteroviruses with an EC50 at a submicromolar efficacy. The mechanism of action of PTC-209HBr was confirmed by time-of-addition, resistance selection and reverse genetics experiments, microscale thermophoresis (MST), viral binding and entry assays, coimmunoprecipitation (Co-IP) and immunofluorescence experiments (IF). Mechanistic studies indicated that PTC-209HBr inhibited EV-A71 infection by impeding the binding between VP1 and the receptor hSCARB2 during the early stage of EV-A71 infection through hindering viral entry into host cells. Collectively, these findings indicated that PCT-209HBr is a novel inhibitor of enteroviruses with a confirmed mechanism of action that can be further developed into EV-A71 DAAs.