Diterpenoids from the Aerial Parts of Isodon serra with Selective Cytotoxic Activity.

Four new diterpenoids, isodosins A-D (1-4), together with nine known compounds (5-13) were isolated and identified from the aerial parts of Isodon serra (Maxim.) Hara. The structures of the new diterpenoids were elucidated based on the analysis of HR-ESI-MS data, 1D/2D-NMR-spectroscopic data, and electronic circular dichroism (ECD) calculations. Cytotoxicities of compounds 2, 3, 5, 6, and 9 against the HepG2 and H1975 cell lines were evaluated with the MTT assay. As a result, compounds 2, 3, and 6 revealed higher levels of cytotoxicity against HepG2 cells than against H1975 cells. Moreover, compund 6 demonstrated the most efficacy in inhibiting the proliferation of HepG2 cells, with an IC50 value of 41.13 ± 3.49 µM. This effect was achieved by inducing apoptosis in a dose-dependent manner. Furthermore, the relationships between the structures and activities of these compounds are briefly discussed.

Two-Drug Combinations Therapy of Different Doses of Valsartan Existing Diverse Significance for Hypertensive Patients.

Background: The incidence of hypertension and clinical complications (e.g., heart, cerebrovascular and kidney injury) is increasing worldwide. It is widely known that a relatively large dose of valsartan (320 mg) could alleviate clinical complications. The current network meta-analysis assessed which drug could be combined with a relatively large dose of valsartan to control blood pressure (BP) more effectively. And which combination therapy with different dosages of valsartan did not induce excessive BP reduction with increasing dosages of valsartan. Methods: The PubMed, Embase, Medline, Cochrane Library, CNKI, Wanfang, and CSTJ databases were searched from inception to October 2022 for relevant randomized controlled trials (RCTs). The search strategies included concepts related to hypertension and two-drug combination therapy of different doses of valsartan, and there were no language or data restrictions. The outcomes included adverse effects and changes in systolic BP and diastolic BP. Permanent discontinuations related to treatment were the most accurate and objective measure of adverse effects. The common adverse effects of most studies (i.e., dizziness, headache, nasopharyngitis, asthenia and urticaria) were also included. A Bayesian network meta-analysis was performed, and mean differences with 95% confidence intervals were calculated. ADDIS and STATA were used for Bayesian model network meta-calculation. Results: Thirty-four RCTs were included involving 26,752 patients, and the interventions included different doses of valsartan combined with various types and doses of drugs. Among many combination therapies, the combination of valsartan 320 mg with amlodipine 10 mg (p < 0.01) had the best antihypertensive effect without significant adverse effects. Compared with valsartan 80 mg and 160 mg, valsartan 320 mg combined with hydrochlorothiazide 25 mg (p > 0.05) did not further reduce BP and was not shown to increase the incidence of adverse effects. Conclusions: Combination therapy with a relatively large dose of valsartan could control BP and improve clinical complications effectively. However, for hypertensive patients with different treatment requirements, specific choices should be made regarding whether to control BP, treat clinical complications, or both.

Outstanding Performance of the Deep Eutectic Solvent-Based Aqueous Biphasic System Constructed with Sodium Citrate for a Green Gold Separation.

Aqueous biphasic systems (ABSs) that are based on deep eutectic solvents (DESs) are environmentally benign systems to use for metal ion separation. In this work, a series of DESs was synthesized for the first time with PEG 400 as hydrogen bond donors and tetrabutylphonium bromide (P4Br), tetrabutylammonium bromide (N4Br), or tetrabutylammonium chloride (N4Cl) as hydrogen bond acceptors, and then they were combined with citrate (Na3C6H5O7), which is eco-friendly, to construct an ABS for use in the separation of Au(I) from an aurocyanide solution. Phase diagrams of DESs + Na3C6H5O7 + H2O systems were constructed using the experimentally measured data. Multiple factors that affect the efficiency of the gold extraction were studied; these factors were the species of salt or DES and their content, the equilibrium pH, the oscillation time, and the initial gold concentration. Gold(I) is preferentially retained in the DES-rich phase, and the P4Br:PEG 1:2 + Na3C6H5O7 + H2O system has a high extraction efficiency of 100.0% under optimized conditions. FT-IR, NMR, and TEM characterizations and DFT calculations show that the migration of Au(I) from the salt-rich to the DES-rich phase follows an ion exchange mechanism. Specifically, Au(CN)2- replaces Br- in the original P4Br and generates a stable ion pair with the quaternary phosphonium salt cation, P+, and this replacement is driven by electrostatic attractions. A new strong hydrogen bond network simultaneously forms between the anionic Au(CN)2- and the -OH group in the PEG 400 component. Finally, the gold of Au(I)-loaded P4Br:PEG 1:2 can be successfully reduced by sodium borohydride with an efficiency of 100.0%. The strategy to extract gold(I) from alkaline cyanide solutions using an ABS based on DESs as proposed in this work provides a potential platform for developing green technology for recovering gold.

Venoarterial extracorporeal membrane oxygenation improves survival in a rat model of acute myocardial infarction.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used in high-risk acute myocardial infarction (AMI) patients with promising outcomes. However, the underlying molecular mechanisms remain unknown and a VA-ECMO animal model has not yet been established. The purpose of this study was to establish a VA-ECMO model in AMI rats and evaluate long-term cardiac function. METHODS: We first established AMI in 20 Sprague-Dawley (SD) rats by ligating the left anterior descending coronary artery, while five rats underwent a thoracotomy to form the sham group. VA-ECMO was established after 30mins of AMI in 10 rats through the right jugular vein for venous drainage and right femoral artery for arterial infusion. Arterial blood pressure was monitored using a catheter in the left femoral artery, blood gas parameters were measured using a blood gas analyzer, while myocardial enzymes were detected using an ELISA Kit. Cardiac function was assessed through echocardiography on day 15. Masson staining and Western Blot were used for evaluating myocardial fibrosis, while histological injury was evaluated using hematoxylin and eosin staining. RESULTS: VA-ECMO support stabilized blood pressure, decreased the levels of myocardial enzymes including cTnI, cTnT, CK-MB, and was associated with a higher survival rate. In the long term, the VA-ECMO group showed improved cardiac function, significantly increased EF and FS but significantly decreased EDV and ESV compared to the AMI group. Furthermore, VA-ECMO significantly alleviated pathological damage and myocardial fibrosis. CONCLUSION: We established an economical, reliable, and reproducible VA-ECMO animal model in AMI rats, and demonstrated that VA-ECMO support prevents deteriorated cardiac function.

Establishment of a venovenous extracorporeal membrane oxygenation in a rat model of acute respiratory distress syndrome.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV ECMO) is now considered a reasonable option to salvage acute respiratory distress syndrome (ARDS). However, we lack a rodent model for experimental studies. This study was undertaken to establish an animal model of VV ECMO in ARDS rats. METHODS: A total of 18 Sprague-Dawley (SD) rats (350 ± 50 g) were used in this study. Using a rat model of oleic acid (OA)-induced ARDS, VV ECMO was established through cavoatrial cannulation of the right jugular vein for venous drainage and venous reinfusion with a specially designed three-cavity catheter. Continuous arterial pressure monitoring was implemented by using a catheter through cannulation of the right femoral artery. The central temperature was monitored with a rectal probe. Arterial blood gas monitoring was implemented by a blood gas analyzer at three-time points: at baseline, 1-hour (after OA modeling), and 3.5-hour (after VV ECMO support). Lung tissue and bronchoalveolar lavage fluid were harvested respectively for protein concentration and pulmonary histologic evaluation to confirm the alleviation of lung injury during VV ECMO. RESULTS: Following ARDS induced by OA, ten rats were successfully established on VV ECMO without failure and survived the ECMO procedure. VV ECMO alleviated lung injury and restored adequate circulation for the return of lung function and oxygenation. VV ECMO was associated with decreased lung injury score, wet/dry weight ratio, and fluid leakage into airspaces. CONCLUSION: We have established a reliable, economical, and functioning ARDS rat model of VV ECMO.

Polycomb-like 2 regulates PRC2 components to affect proliferation in glioma cells.

INTRODUCTION: The Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis. The PcG mainly consists of two complexes, PRC1 and Polycomb Repressive Complex 2 (PRC2). Polycomb-like 2 (PCL2) is known to interact with the PRC2 protein. The role of PCL2 in the development and progression of glioma is unclear. METHODS: We use The Cancer Genome Atlas (TCGA) database to detect the expression of PCL2 in various tumors. 117 cases of clinical glioma (WHOI-IV) were collected, and PCL2 expression and localization were detected by immunohistochemical staining. Glioma cells U87/U251 were infected with overexpressed and interfered PCL2. CCK8 assay, colony formation assay, EdU method, cell cycle and apoptosis were used to detect cell proliferation and apoptosis. Western blot was used to detect the expression of PRC2-related core proteins. After DZNeP intervention, PRC2 protein expression was again measured to discuss the mechanism of PCL2 action. RESULTS: TCGA database results and immunohistochemical staining results suggest that PCL2 is highly expressed in gliomas. We found that the PCL2 gene promoted tumor cell proliferation, enhanced the colony formation ability, and increased S phase in the cell cycle. The overexpression of PCL2 upregulated the expression levels of EZH2 and EED (two core members of PRC2), decreased the expression of SUZ12, increased the level of H3K27 trimethylation (H3K27me3), H3K4 dimethylation (H3K4me2), and decreased H3K9 dimethylation (H3K9me2). The result after interfering with PCL2 was the opposite. CONCLUSIONS: As an important accessory protein of PRC2, PCL2 can not only change the expression of PRC2 components, but also affect the expression level of Histone methylation. Therefore, PCL2 may be an important hub for regulating the synergy among PRC2 members. This study revealed PCL2 as a new target for tumor research and open up a new avenue for future research in glioma.

Effect of ferric chloride on phosphorus immobilization and speciation in Dianchi Lake sediments.

Immobilization of phosphorus in lake sediments and control of internal-loading phosphorus release have become crucial aspects of eutrophication lake management. In this study, the immobilization efficiency of phosphorus by ferric chloride in Dianchi Lake sediments was investigated. In addition, effects of the dosage of ferric chloride and contact time on the release of phosphorus from sediments were investigated. Laboratory experiments revealed that ferric chloride can effectively inhibit the release of phosphorus from sediments. At a ferric chloride dosage of 10 mg/g, the total phosphorus concentration of the overlying water was reduced by ~87%. With the increase in the contact time, the amount of phosphorus immobilized by ferric chloride increased. To further evaluate the feasibility of ferric chloride for immobilising phosphorus in sediments, an amplification experiment with a water volume of 50 L was carried out. By the addition of 6 mg/g of ferric chloride, the total phosphorus concentration of the overlying water was still less than 0.01 mg/L after 100 days. At the same time, the phosphorus species in the sediment after treatment with ferric chloride were analyzed. Results revealed that ferric chloride mainly converts unstable exchangeable phosphorus (Ex-P), ferric phosphate (Fe-P) and organic phosphorus (Or-P) into more stable occluded phosphate (O-P), reducing the possible release of phosphorus from sediments. Practical applications of ferric chloride to control the release of phosphorus from Dianchi Lake sediments were discussed.

Improvement of the process of removing phosphorus from high-phosphorus distillery effluent by ferric chloride using response surface methodology and three-step method.

The purpose of this study was to optimize the coagulation-flocculation effect of a wastewater treatment system using the response surface methodology (RSM) and three-step method to minimize phosphorus concentration in the distillate wastewater. In order to minimize the concentration of total phosphorus (TP), experiments were carried out using 33-factorial designs with three levels and three factors. A Box-Behnken design, which is the standard design of RSM, was used to evaluate the effects and interactions of three major factors (Fe:P (w/w) ratio, coagulation pH and fast mixing speed (FMS)) on the treatment efficiency. A multivariable quadratic model developed for studying the response indicated that the values for optimum conditions for Fe:P (w/w) ratio, coagulation pH and FMS were 2.40, 6.48 and 100 rev min-1, respectively. Under optimal process conditions, the TP concentration in the distillery effluent was reduced from 10 mg L-1 to 0.215 mg L-1, representing a removal efficiency of 97.85%. Based upon the statistical evaluation of results, it is inferred that RSM can be used as an appropriate approach to optimize the coag-flocculation process. Meanwhile, the study has shown that, for the equivalent dose of ferric chloride, the average three-step effect is better than that of the one-time addition.

CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions.

Enhancer regions and transcription start sites of estrogen-target regulated genes are connected by means of Estrogen Receptor long-range chromatin interactions. Yet, the complete molecular mechanisms controlling the transcriptional output of engaged enhancers and subsequent activation of coding genes remain elusive. Here, we report that CTCF binding to enhancer RNAs is enriched when breast cancer cells are stimulated with estrogen. CTCF binding to enhancer regions results in modulation of estrogen-induced gene transcription by preventing Estrogen Receptor chromatin binding and by hindering the formation of additional enhancer-promoter ER looping. Furthermore, the depletion of CTCF facilitates the expression of target genes associated with cell division and increases the rate of breast cancer cell proliferation. We have also uncovered a genomic network connecting loci enriched in cell cycle regulator genes to nuclear lamina that mediates the CTCF function. The nuclear lamina and chromatin interactions are regulated by estrogen-ER. We have observed that the chromatin loops formed when cells are treated with estrogen establish contacts with the nuclear lamina. Once there, the portion of CTCF associated with the nuclear lamina interacts with enhancer regions, limiting the formation of ER loops and the induction of genes present in the loop. Collectively, our results reveal an important, unanticipated interplay between CTCF and nuclear lamina to control the transcription of ER target genes, which has great implications in the rate of growth of breast cancer cells.

High Throughput Chemical Screening Reveals Multiple Regulatory Proteins on FOXA1 in Breast Cancer Cell Lines.

Forkhead box A1 (FOXA1) belongs to the forkhead class transcription factor family, playing pioneering function for hormone receptors in breast and prostate cancers, and mediating activation of linage specific enhancers. Interplay between FOXA1 and breast cancer specific signaling pathways has been reported previously, indicating a regulation network on FOXA1 in breast cancer cells. Here in this study, we aimed to identify which are the proteins that could potentially control FOXA1 function in breast cancer cell lines expressing different molecular markers. We first established a luciferase reporter system reflecting FOXA1 binding to DNA. Then, we applied high throughput chemical screening of multiple protein targets and mass spectrometry in breast cancer cell lines expressing different molecular markers: ER positive/HER2 negative (MCF-7), ER positive/HER2 positive (BT474), and ER negative/HER2 positive (MDA-MB-453). Regardless of estrogen receptor status, HER2 (human epidermal growth factor receptor 2) enriched cell lines showed similar response to kinase inhibitors, indicating the control of FOXA1 by cell signaling kinases. Among these kinases, we identified additional receptor tyrosine kinases and cyclin-dependent kinases as regulators of FOXA1. Furthermore, we performed proteomics experiments from FOXA1 inmunoprecipitated protein complex to identify that FOXA1 interacts with several proteins. Among all the targets, we identified cyclin-dependent kinase 1 (CDK1) as a positive factor to interact with FOXA1 in BT474 cell line. In silico analyses confirmed that cyclin-dependent kinases might be the kinases responsible for FOXA1 phosphorylation at the Forkhead domain and the transactivation domain. These results reveal that FOXA1 is potentially regulated by multiple kinases. The cell cycle control kinase CDK1 might control directly FOXA1 by phosphorylation and other kinases indirectly by means of regulating other proteins.

MicroRNA-33a disturbs influenza A virus replication by targeting ARCN1 and inhibiting viral ribonucleoprotein activity.

In order to explore the roles of microRNA(s) [miRNA(s)] in the influenza A virus life cycle, we compared the miRNA profiles of 293T and HeLa cell lines, as influenza A virus can replicate efficiently in 293T cells but only poorly in HeLa cells. We analysed differentially expressed miRNAs and identified five, including miR-33a, that could disturb influenza A virus replication significantly. Using TargetScan analysis, we found that ARCN1 could be a potential target of miR-33a. To confirm whether miR-33a could truly target ARCN1, we generated a luciferase reporter for the ARCN1 3' untranslated region (UTR) and performed a luciferase assay. The data indicated that miR-33a could suppress the luciferase activity of the reporter for the ARCN1 3' UTR but not a reporter in which the predicted miR-33a targeting sites on ARCN1 3' UTR were mutated. We performed immunoblotting to confirm that miR-33a could downregulate the protein level of ARCN1. Consistently, the level of ARCN1 protein in HeLa cells was significantly lower than that in 293T cells. We also demonstrated that ectopic expression of ARCN1 could partially rescue the inhibitory effect of miR-33a on virus replication. Furthermore, we demonstrated that miR-33a could impede virus replication at the stage of virus internalization, which was similar to the pattern for knockdown of ARCN1, indicating that miR-33a inhibits influenza virus infection by suppressing ARCN1 expression. In addition, we found that miR-33a could also weaken the viral ribonucleoprotein activity in an ARCN1-independent manner. In conclusion, we found that miR-33a is a novel inhibitory factor for influenza A virus replication.

Commentary on "Arsenic mobility in the arsenic-contaminated Yangzonghai Lake in China" by Changliang Yang et al. [Ecotoxicology and Environmental Safety, 107(2014)321-327].

This commentary concerns some inaccuracy in recently published paper "Arsenic mobility in the arsenic-contaminated Yangzonghai Lake in China". Yang et al. raised an incorrect conclusion that after treatment with FeCl3 using the flocculation method, the sediments in the Yangzonghai Lake released As in the summer. The fundamental flaws of the paper which led to the incorrect conclusion were unreasonable sampling method for determining As concentration at various water depth and the wrong lake water volume of 6.04×10(8)m(3) (actually 4.8×10(8)m(3)) for calculating inventory of As in Yangzhonghai in August 2012. Then the authors attribute the As release in summer to the high concentration of HCO3(-) without any support of experimental data. Meanwhile, the authors designed a microbiological experiment to illustrate that increasing capacity of anaerobic microorganism could lead to As releasing from sediments. In our view point, this microbiological experiment was nonsense for evaluating the stability of As in sediments of Yangzonghai lake since the experimental conditions were greatly different from the natural conditions. Therefore, we conclude that the conclusions put forward by YANG are incorrect.

Arsenic pollution and its treatment in Yangzonghai lake in China: In situ remediation.

In this study, the effect of direct atomization and spraying a ferric chloride (FeCl3) solution to decrease the arsenic concentration and its pollution in Yangzonghai Lake, China, was investigated. Ten ships were used for spraying 6-8t of FeCl3 in the lake every day since October 2009. After spraying, the average concentration of arsenic in Yangzonghai Lake, which has an area of 31 km(2), an average depth of 20 m, and a water storage capacity of 604 million m(3), started to decrease from 0.117 mg L(-1). On 20 September 2010, the lowest arsenic level of 0.021 mg L(-1) was attained, with an arsenic removal rate as high as 82.0%. However, the source of pollution was not eliminated, and local rainfall mainly occurred in September; hence, arsenic concentration from October to December increased to 0.078 mg L(-1). At the beginning of 2011, the As concentration decreased and remained at 0.025-0.028 mg L(-1) from May to September. During the 2 years of FeCl3 treatment, the water quality improved from V Class to II-III Class of the Chinese standards, which remained consistent for 12 months. The total cost for this in situ water treatment was 29 million RMB, which was less than a hundredth of the expected expenditure of 4-7 billion RMB. The treatment method achieved goals such as high arsenic removal rate, easy operation, low cost, and ecological security. In this study, the changing patterns of the concentration of arsenic in Yangzonghai Lake from June 2008 to December 2014 were analyzed, and the following problems were discussed: the stability of iron-arsenic precipitates in the lake, the concentrations of ferric and chloride ions in the lake, the pH of the lake during treatment, the stability of iron-arsenic precipitates in the lakebed sediments, and the variation of phytoplankton species in the lake.

[Mechanism of gold solid extraction from aurocyanide solution using D3520 resin impregnated with TRPO].

Trialkyphosphine oxides (TRPO) was successfully used for the impregnation of D3520 resin to prepare an extractant-impregnated resin (EIR). Solid extraction of Au(I) from alkaline cyanide solution was studied using this extractant-impregnated resin (EIR), with addition of cetyltrimethylammonium bromide (CTMAB), directly into the aurous aqueous phase in advance. The mechanism of solid extraction was further investigated by means of FTIR, XPS and SEM. The column separation studies have shown that cationic surfactant CTMAB played a key role in the solid phase extraction, and the resin containing TRPO were effective for the extraction of gold when the molar ratio of CTMAB: Au( I ) reached 1:1. FTIR spectroscopy of gold loaded EIR showed that the frequency of C[triple bond]N stretching vibration was at 2144 cm(-1), and the frequency of P=O stretching vibration shifted to lower frequency from 1153 to 1150 cm(-1). The XPS spectrum of N(1s), Au(4f7/2) and Au(4f5/2) sugges- ted that the coordination environment of gold did not change before and after extraction, and gold was still as the form of Au (CN)2(-) anion exiting in the loaded resin; O(1s) spectrum showed that the chemically combined water significantly increased after solid extraction from 30.74% to 42.34%; Comparing to the P(2p) spectrum before and after extraction, the binding energy increased from 132. 15 to 132. 45 eV, indicating there maybe existing hydrogen-bond interaction between P=O and water molecule, such as P=O...H-O-H. The above results obtained established that in the solid extraction process, the hydrophobic ion association [CTMA+ x Au(CN)] diffused from the bulk solution into the pores of the EIR, and then be solvated by TRPO adsorbed in the pores through hydrogen bonding bridged by the water molecules.

Efficacy of ultrasound-guided radiofrequency ablation of papillary thyroid microcarcinoma after one year.

OBJECTIVE: This study aims to evaluate the feasibility and safety of percutaneous radiofrequency ablation guided by ultrasound for treating papillary thyroid microcarcinoma. METHOD: At our institution, fifty people who had been treated for micropapillary thyroid cancer with ultrasound-guided radiofrequency ablation were chosen. Thyroid function was evaluated after one month, and the volume of the ablation region was assessed immediately, 3, 6, and 12 months after treatment. At the same time, the complications or adverse reactions after treatment were evaluated. RESULTS: As time passed, the volume of the ablation area decreased gradually, showing a regression trend. There was a significant difference in the volume of the ablation area between adjacent groups (P < 0.05), and the tumor volume reduction ratio (VRR) of the ablation area was a statistically significant difference between adjacent groups (P < 0.05). There was no significant difference between the indexes related to thyroid function before and after treatment(P > 0.05). No local recurrence or distant metastasis was found during follow-up; The most common complication after the operation was a slight pain in the neck. A few patients had toothache and neck swelling symptoms, and the above symptoms subsided within 24 h after the operation. CONCLUSION: Ultrasound-guided radiofrequency ablation is safe and effective for treating single-focus micropapillary thyroid carcinoma while retaining thyroid function, with few and minor complications, which can be used as an ideal surgical option.

Additively-Manufactured Broadband Metamaterial-Based Luneburg Lens for Flexible Beam Scanning.

Multi-beam microwave antennas have attracted enormous attention owing to their wide range of applications in communication systems. Here, we propose a broadband metamaterial-based multi-beam Luneburg lens-antenna with low polarization sensitivity. The lens is constructed from additively manufactured spherical layers, where the effective permittivity of the constituting elements is obtained by adjusting the ratio of dielectric material to air. Flexible microstrip patch antennas operating at different frequencies are used as primary feeds illuminating the lens to validate the radiation features of the lens-antenna system. The proposed Luneburg lens-antenna achieves ±72° beam scanning angle over a broad frequency range spanning from 2 GHz to 8 GHz and presents a gain between 15.3 dBi and 22 dBi, suggesting potential applications in microwave- and millimeter-wave mobile communications, radar detection and remote sensing.

High-performance fentanyl molecularly imprinted electrochemical sensing platform designed through molecular simulations.

BACKGROUND: Fentanyl and its derivatives are a type of potent opioid analgesics, with the characteristics of diverse structure, high toxicity, extremely low content, and high fatality rate. Currently, they have become one of the most serious problems in international drug abuse control due to their extensive use in drug production and use. Therefore, the development of a rapid, sensitive, and accurate method for detecting trace fentanyl is of great significance. In this study, in view of its complex structure and trace concentration, a new molecular imprinting electrochemical sensor was developed through molecular simulations followed by experimental validation to detect trace fentanyl. RESULTS: The process consisted of first obtaining the optimal functional monomer and its molar ratio through molecular simulations. The recognition sites of fentanyl-imprinted polymers were predicted to guide the synthesis of imprinted membranes with precision approach to ensure an efficient and accurate reaction process. Reduced graphene oxide (ErGO) was then deposited on glassy carbon electrode surface by electrochemical reduction to yield large numbers of active sites suitable for catalyzing reactions of fentanyl piperidine for promoted efficient electron transfer and amplified sensitivity of the sensor. Accordingly, fentanyl molecularly imprinted film was formed through one-step electropolymerization to yield greatly improved sensing selectivity due to the specific recognition of molecularly imprinted polymer. Under optimal experimental conditions, the fentanyl sensor showed an extended detection range of 3.84 × 10-9 mol L-1-1.72 × 10-6 mol L-1 and a detection limit of 1.28 × 10-9 mol L-1. SIGNIFICANCE: A distinctive feature of this sensor is its molecularly imprinted polymerized membrane, which offers excellent specific recognition, thereby boosting the sensor's selectivity. Throughout the sensor's development process, molecular simulations were employed to steer the synthesis of molecularly imprinted polymers and predict the recognition sites of fentanyl-imprinted polymers. The experimental outcomes proved to align with the simulation data. The final sensor exhibited outstanding selectivity, repeatability, stability, and high sensitivity. The sensor was effectively used to reliably track fentanyl in human serum samples, with acceptable analytical reliability, suggesting its potential for practical applications.

Symptomatic HIV infection and in-hospital outcomes for patients with acute myocardial infarction undergoing percutaneous coronary intervention from national inpatient sample.

Human immunodeficiency virus (HIV) infection increases the risk of acute myocardial infarction (AMI). However, little is known about its association with in-hospital outcomes and temporal trends in patients with AMI undergoing percutaneous coronary intervention (PCI). We queried patients with AMI who underwent PCI from the National Inpatient Sample Database (2003-2015) and stratified them into three groups: symptomatic, asymptomatic, and HIV-negative. After 1:2 case-control matching (CCM), logistic regression analysis was conducted to determine how HIV infection affected in-hospital outcomes. We also evaluated their recent trends from 2003 to 2015. The total weighted national estimate of 2,191,129 AMI cases included 2,178,995 HIV/AIDS-negative, 4994 asymptomatic, and 7140 symptomatic HIV cases. Symptomatic but not asymptomatic patients with HIV suffered more than triple the in-hospital mortality (adjusted odds ratio (aOR) 3.6, 95% confidence interval (CI) 2.5-5.2), over one-fold incidence of acute kidney injury (aOR 2.6 95% CI 1.9-3.4) and cardiogenic shock risk (aOR 1.9, 95% CI 1.3-2.7), a longer length of hospital stay (beta 1.2, 95% CI 1.0-1.5), and had more procedures (beta 1.3, 95% CI 1.2-1.5). These disparities relating to symptomatic HIV infection persisted from 2003 to 2015. In patients with AMI who underwent PCI, symptomatic HIV infection was associated with higher in-hospital mortality and more severe outcomes.

Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis.

Introduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatment guidelines for Rifampicin-resistant spinal TB (DSTB) contribute significantly to the obstacles in its effective management. Consequently, there is an urgent need for innovative and efficacious drugs to address Rifampicin-resistant spinal tuberculosis, minimizing the duration of therapy sessions. This study aims to investigate potential targets for DSTB through comprehensive proteomic and pharmaco-transcriptomic analyses. Methods: Mass spectrometry-based proteomics analysis was employed to validate potential DSTB-related targets. PPI analysis confirmed by Immunohistochemistry (IHC) and Western blot analysis. Results: The proteomics analysis revealed 373 differentially expressed proteins (DEPs), with 137 upregulated and 236 downregulated proteins. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses delved into the DSTB-related pathways associated with these DEPs. In the context of network pharmacology analysis, five key targets-human leukocyte antigen A chain (HLAA), human leukocyte antigen C chain (HLA-C), HLA Class II Histocompatibility Antigen, DRB1 Beta Chain (HLA-DRB1), metalloproteinase 9 (MMP9), and Phospholipase C-like 1 (PLCL1)-were identified as pivotal players in pathways such as "Antigen processing and presentation" and "Phagosome," which are crucially enriched in DSTB. Moreover, pharmaco-transcriptomic analysis can confirm that 58 drug compounds can regulate the expression of the key targets. Discussion: This research confirms the presence of protein alterations during the Rifampicin-resistant process in DSTB patients, offering novel insights into the molecular mechanisms underpinning DSTB. The findings suggest a promising avenue for the development of targeted drugs to enhance the management of Rifampicin-resistant spinal tuberculosis.

[Colletodiol inhibits the replication of influenza A virus WSN/H1N1 by reducing the activity of viral RNA polymerase].

OBJECTIVE: To screen for compounds against influenza A virus by using the viral promoter reporter cell line HeLa-IAV-Luc and investigate their anti-viral mechanism. METHODS: We screened the inhibitors of influenza A virus by infecting HeLa-IAV-Luc cells with influenza A virus WSN/H1N1 and treating it with the compounds isolated from microbial metabolites. The cell lysates were then subjected to the luciferase assay. We conducted the pesudovirus assay to analyze whether the compound affected the function of hemagglutinin (HA). We carried out the influenza viral promoter reporter assay to examine whether the compound could inhibitinfluenza viral RNA polymerase (vRNP) activity. The effect of anti-viral compoundon influenza viral RNA synthesis was measured by real-time fluorescence quantitative PCR. RESULTS: Colletodiol inhibited the replication of influenza A virus in HeLa-IAV-Luc cells by luciferase assay. It did not inhibit the function of HA protein based on the results of the time-of-addition experiment and pseudovirus assay. The influenza viral polymerase promoter reporter assay indicated that Colletodiol could inhibit the activity of vRNP dramatically. Due to the inhibition of vRNP, the influenza viral RNA synthesis decreased significantly. CONCLUSION: Compound Colletodiol was an inhibitor of influenza A virus. It blocks the replication of influenza A virus by reducing the activity of vRNP.