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1.
Chemistry ; : e202401293, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828487

ABSTRACT

Herein, we report a general copper-catalyzed method for the tunable oxygenative rearrangement of tetrahydrocarbazoles to cyclopentyl-bearing spiroindolin-2-ones and spiroindolin-3-ones. The method demonstrates excellent chemoselectivity, regioselectivity, and product control simply by using the H2O and O2 as oxygen source, respectively. This open-flask method is safe and simple to operate, and no other chemical oxidants are required. Besides, inspired from the unique pathway of 1, 2-migration rearrangement, a highly controllable hydroxylation of indoles for the construction of C3a-hydroxyl iminium indolines was also developed. Mechanistic experiments suggest that a single-electron transfer-induced oxidation process is responsible for the tunable selectivity control.

2.
World J Gastroenterol ; 30(18): 2440-2453, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38764767

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) with hepatic histological NAFLD activity score ≥ 4 and fibrosis stage F ≥ 2 is regarded as "at risk" non-alcoholic steatohepatitis (NASH). Based on an international consensus, NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), respectively; hence, we introduced the term "high-risk MASH". Diagnostic values of seven non-invasive models, including FibroScan-aspartate transaminase (FAST), fibrosis-4 (FIB-4), aspartate transaminase to platelet ratio index (APRI), etc. for high-risk MASH have rarely been studied and compared in MASLD. AIM: To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH. METHODS: A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital, between January 2012 and December 2020. After screening for MASLD and the exclusion criteria, 279 patients were included and categorized into high-risk and non-high-risk MASH groups. Utilizing threshold values of each model, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), were calculated. Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve (AUROC). RESULTS: MASLD diagnostic criteria were met by 99.4% patients with NAFLD. The MASLD population was analyzed in two cohorts: Overall population (279 patients) and the subgroup (117 patients) who underwent liver transient elastography (FibroScan). In the overall population, FIB-4 showed better diagnostic efficacy and higher PPV, with sensitivity, specificity, PPV, NPV, and AUROC of 26.9%, 95.2%, 73.5%, 72.2%, and 0.75. APRI, Forns index, and aspartate transaminase to alanine transaminase ratio (ARR) showed moderate diagnostic efficacy, whereas S index and gamma-glutamyl transpeptidase to platelet ratio (GPR) were relatively weaker. In the subgroup, FAST had the highest diagnostic efficacy, its sensitivity, specificity, PPV, NPV, and AUROC were 44.2%, 92.3%, 82.1%, 67.4%, and 0.82. The FIB-4 AUROC was 0.76. S index and GPR exhibited almost no diagnostic value for high-risk MASH. CONCLUSION: FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI, Forns index, ARR, S index, and GPR; FAST is superior to FIB-4.


Subject(s)
Aspartate Aminotransferases , Elasticity Imaging Techniques , Liver , Non-alcoholic Fatty Liver Disease , Predictive Value of Tests , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/pathology , Male , Female , Middle Aged , Retrospective Studies , Aspartate Aminotransferases/blood , Elasticity Imaging Techniques/methods , Liver/pathology , Liver/diagnostic imaging , Adult , Biopsy , ROC Curve , Platelet Count , Sensitivity and Specificity , Severity of Illness Index , Aged , Biomarkers/blood , Risk Factors , Risk Assessment/methods
3.
Antimicrob Agents Chemother ; 68(4): e0126123, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38415983

ABSTRACT

Antibiotic resistance represents a significant challenge to public health and human safety. The primary driver behind the dissemination of antibiotic resistance is the horizontal transfer of plasmids. Current conjugative transfer assay is generally performed in a standardized manner, ignoring the effect of the host environment. Host defense peptides (HDPs) possess a wide range of biological targets and play an essential role in the innate immune system. Herein, we reveal that sub-minimum inhibitory concentrations of HDPs facilitate the conjugative transfer of RP4-7 plasmid in the Luria Broth medium, and this observation is reversed in the RPMI medium, designed to simulate the host environment. Out of these HDPs, indolicidin (Ind), a cationic tridecapeptide from bovine neutrophils, significantly inhibits the conjugation of multidrug resistance plasmids in a dose-dependent manner, including blaNDM- and tet(X4)-bearing plasmids. We demonstrate that the addition of Ind to RPMI medium as the incubation substrate downregulates the expression of conjugation-related genes. In addition, Ind weakens the tricarboxylic acid cycle, impedes the electron transport chain, and disrupts the proton motive force, consequently diminishing the synthesis of adenosine triphosphate and limiting the energy supply. Our findings highlight the importance of the host-like environments for the development of horizontal transfer inhibitors and demonstrate the potential of HDPs in preventing the spread of resistance plasmids.


Subject(s)
Conjugation, Genetic , Genes, Bacterial , Animals , Cattle , Humans , Plasmids/genetics , Drug Resistance, Microbial , Gene Transfer, Horizontal , Antimicrobial Cationic Peptides/pharmacology , Anti-Bacterial Agents/pharmacology
4.
Sci Rep ; 13(1): 19836, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37963966

ABSTRACT

Emerging infectious diseases are a critical public health challenge in the twenty-first century. The recent proliferation of such diseases has raised major social and economic concerns. Therefore, early detection of emerging infectious diseases is essential. Subjects from five medical institutions in Beijing, China, which met the spatial-specific requirements, were analyzed. A quality control process was used to select 37,422 medical records of infectious diseases and 56,133 cases of non-infectious diseases. An emerging infectious disease detection model (EIDDM), a two-layer model that divides the problem into two sub-problems, i.e., whether a case is an infectious disease, and if so, whether it is a known infectious disease, was proposed. The first layer model adopts the binary classification model TextCNN-Attention. The second layer is a multi-classification model of LightGBM based on the one-vs-rest strategy. Based on the experimental results, a threshold of 0.5 is selected. The model results were compared with those of other models such as XGBoost and Random Forest using the following evaluation indicators: accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. The prediction performance of the first-layer TextCNN is better than that of other comparison models. Its average specificity for non-infectious diseases is 97.57%, with an average negative predictive value of 82.63%, indicating a low risk of misdiagnosing non-infectious diseases as infectious (i.e., a low false positive rate). Its average positive predictive value for eight selected infectious diseases is 95.07%, demonstrating the model's ability to avoid misdiagnoses. The overall average accuracy of the model is 86.11%. The average prediction accuracy of the second-layer LightGBM model for emerging infectious diseases reaches 90.44%. Furthermore, the response time of a single online reasoning using the LightGBM model is approximately 27 ms, which makes it suitable for analyzing clinical records in real time. Using the Knox method, we found that all the infectious diseases were within 2000 m in our case, and a clustering feature of spatiotemporal interactions (P < 0.05) was observed as well. Performance testing and model comparison results indicated that the EIDDM is fast and accurate and can be used to monitor the onset/outbreak of emerging infectious diseases in real-world hospitals.


Subject(s)
Communicable Diseases, Emerging , Communicable Diseases , Noncommunicable Diseases , Humans , Communicable Diseases, Emerging/diagnosis , Communicable Diseases, Emerging/epidemiology , Communicable Diseases/diagnosis , Communicable Diseases/epidemiology , Disease Outbreaks , Algorithms
5.
Ecotoxicol Environ Saf ; 262: 115124, 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37327521

ABSTRACT

The emergence and rapid spread of antibiotic resistance seriously compromise the clinical efficacy of current antibiotic therapies, representing a serious public health threat worldwide. Generally, drug-susceptible bacteria can acquire antibiotic resistance through genetic mutation or gene transfer, among which horizontal gene transfer (HGT) plays a dominant role. It is widely acknowledged that the sub-inhibitory concentrations of antibiotics are the key drivers in promoting the transmission of antibiotic resistance. However, accumulating evidence in recent years has shown that in addition to antibiotics, non-antibiotics can also accelerate the horizontal transfer of antibiotic resistance genes (ARGs). Nevertheless, the roles and potential mechanisms of non-antibiotic factors in the transmission of ARGs remain largely underestimated. In this review, we depict the four pathways of HGT and their differences, including conjugation, transformation, transduction and vesiduction. We summarize non-antibiotic factors accounting for the enhanced horizontal transfer of ARGs and their underlying molecular mechanisms. Finally, we discuss the limitations and implications of current studies.

6.
J Hazard Mater ; 453: 131428, 2023 07 05.
Article in English | MEDLINE | ID: mdl-37094448

ABSTRACT

The propagation of antimicrobial resistance (AMR) is constantly paralyzing our healthcare systems. In addition to the pressure of antibiotic selection, the roles of non-antibiotic compounds in disseminating antibiotic resistance genes (ARGs) are a matter of great concerns. This study aimed to explore the impact of different disinfectants on the horizontal transfer of ARGs and their underlying mechanisms. First, the effects of different kinds of disinfectants on the conjugative transfer of RP4-7 plasmid were evaluated. Results showed that quaternary ammonium salt, organic halogen, alcohol and guanidine disinfectants significantly facilitated the conjugative transfer. Conversely, heavy-metals, peroxides and phenols otherwise displayed an inhibitory effect. Furthermore, we deciphered the mechanism by which guanidine disinfectants promoted conjugation, which includes increased cell membrane permeability, over-production of ROS, enhanced SOS response, and altered expression of conjugative transfer-related genes. More critically, we also revealed that guanidine disinfectants promoted bacterial energy metabolism by enhancing the activity of electron transport chain (ETC) and proton force motive (PMF), thus promoting ATP synthesis and flagellum motility. Overall, our findings reveal the promotive effects of disinfectants on the transmission of ARGs and highlight the potential risks caused by the massive use of guanidine disinfectants, especially during the COVID-19 pandemic.


Subject(s)
COVID-19 , Disinfectants , Humans , Anti-Bacterial Agents/pharmacology , Disinfectants/pharmacology , Genes, Bacterial , Pandemics , Drug Resistance, Microbial/genetics , Guanidines , Gene Transfer, Horizontal , Plasmids/genetics
7.
Med Res Rev ; 43(4): 1068-1090, 2023 07.
Article in English | MEDLINE | ID: mdl-36896761

ABSTRACT

Novel antibacterial therapies are urgently required to tackle the increasing number of multidrug-resistant pathogens. Identification of new antimicrobial targets is critical to avoid possible cross-resistance issues. Bacterial proton motive force (PMF), an energetic pathway located on the bacterial membrane, crucially regulates various biological possesses such as adenosine triphosphate synthesis, active transport of molecules, and rotation of bacterial flagella. Nevertheless, the potential of bacterial PMF as an antibacterial target remains largely unexplored. The PMF generally comprises electric potential (ΔΨ) and transmembrane proton gradient (ΔpH). In this review, we present an overview of bacterial PMF, including its functions and characterizations, highlighting the representative antimicrobial agents that specifically target either ΔΨ or ΔpH. At the same time, we also discuss the adjuvant potential of bacterial PMF-targeting compounds. Lastly, we highlight the value of PMF disruptors in preventing the transmission of antibiotic resistance genes. These findings suggest that bacterial PMF represents an unprecedented target, providing a comprehensive approach to controlling antimicrobial resistance.


Subject(s)
Anti-Infective Agents , Proton-Motive Force , Humans , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial
8.
Appl Opt ; 61(25): 7401-7408, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36256041

ABSTRACT

Streak tube imaging lidar (STIL) can obtain 4-D images of a target, and its performance is mainly determined by the streak tube sensor. To obtain a large field of view, we developed a streak tube with a photocathode length as large as 35.3 mm, which is larger than the commonly used ST-HDR (30 mm). At the same time, the temporal resolution and dynamic spatial resolution are 60 ps and 12 lp/mm, which are very suitable to obtain accurate target coordinates for 4-D imaging. In addition, the streak tube has a high detection sensitivity of 46 mA/W at 500 nm and, hence, prospects in remote imaging. To test the performance of the streak tube, an underwater STIL experiment was conducted. Echo signal processing was performed by means of a bandpass filter and a matched filter, and then the peak detection algorithm was used to reconstruct the image. The results indicate that a spatial resolution better than 9 mm is achieved in the limpid water with a depth of 20 m, and a range accuracy of 1 cm is achieved in the turbid water with a depth of 10 m. Such a performance suggests that the large-field streak tube is of great potential for underwater target imaging and other remote imaging applications.


Subject(s)
Algorithms , Tomography, X-Ray Computed , Tomography, X-Ray Computed/methods , Signal Processing, Computer-Assisted , Water
9.
Front Psychol ; 13: 909269, 2022.
Article in English | MEDLINE | ID: mdl-36186336

ABSTRACT

Online education has advantages during COVID-19, but it also has problems related to hardware support and user experience. Focusing on teaching quality by discipline is an effective way to improve teaching quality in universities. To investigate the online education experience from the perspective of different academic disciplines, we evaluated 251,929 student questionnaires and 13,695 teacher questionnaires from 334 universities in China. The main finding was a difference in teaching preparation, experience, feedback, and improvement processes by disciplines. Teachers and students had obvious disciplinary differences in preparation, school support, and teaching constraints. However, disciplinary differences were minor for pedagogical issues such as participation, assignments, and grading, as well as for evaluation of platform technical support and views on the continuation of online learning. The research results analyzed the teaching psychology of teachers and students in different disciplines during the pandemic. Therefore, it explained the impact and role of discipline differences on students' learning psychology during COVID-19. This research will benefit educators, researchers, and policy makers to help them with the improvement of online education.

10.
Comput Intell Neurosci ; 2022: 7671810, 2022.
Article in English | MEDLINE | ID: mdl-35330603

ABSTRACT

The increasing maturity of Internet information technology has led to the rapid rise of blockchain technology. In essence, a blockchain is a shared database. In recent years, blockchain technology has attracted the attention of the public and society. With the continuous development of the market economy, many domestic enterprises have grown in size. At the same time, companies are also faced with various risks, and business risks will have a great impact on the company's production. This article aims to prevent the business risk of Internet information security platform enterprises based on blockchain technology. Through the PoS algorithm, PoW algorithm, secure hash algorithm, and the principle of direct trust, the Internet information security platform is designed. Firstly, the platform is used for a business risk test with a small company, and the platform satisfaction survey is conducted on the employees of the company. The test results show that the subplatform design reduces the business risk of the company by 5%-10%, and employee satisfaction is high. The signature simulation of this algorithm under the same conditions as the SMRA and RSAR methods is also carried out. The results show that the performance of this algorithm is better. This study opens up a new path for small and medium-sized enterprises to prevent business risks.


Subject(s)
Blockchain , Algorithms , Commerce , Internet , Technology
11.
Pharmacol Res ; 175: 105978, 2022 01.
Article in English | MEDLINE | ID: mdl-34813930

ABSTRACT

The widespread dissemination of antibiotic resistance genes (ARGs) is a serious problem and constitutes a threat for public health. Plasmid-mediated conjugative transfer of ARGs is recognized as one of the most important pathways accounting for this global crisis. Inhibiting the conjugative transfer of resistant gene-bearing plasmids provides a feasible strategy to prevent the spread of antibiotic resistance. Here we found that melatonin, a neurohormone secreted from pineal gland, substantially inhibited the horizontal transfer of RP4-7 plasmid in a dose-dependent manner. Furthermore, melatonin could also suppress the conjugal frequency of different types of clinical plasmids that carrying colistin resistance gene mcr-1 rather than blaNDM or tet(X) genes. Next, we investigated the mechanisms underlying the inhibitory effect of melatonin on conjugation. As a result, we showed that the addition of melatonin markedly reduced bacterial membrane permeability and inhibited the oxidative stress. In line with these observations, the conjugative transfer-related genes were regulated accordingly. Most importantly, we uncovered that melatonin disrupted bacterial proton motive force (PMF), which is an essential bacterial energy metabolism substance and is important for conjugative process. Collectively, these results provide implications that some non-antibiotics such as melatonin are effective inhibitors of transmission of ARGs and raise a promising strategy to confront the increasing resistant infections.


Subject(s)
Drug Resistance, Microbial/genetics , Melatonin/pharmacology , Proton-Motive Force/drug effects , Adenosine Triphosphate/metabolism , Ampicillin , Animals , Anti-Bacterial Agents , Cell Membrane Permeability/drug effects , Chloramphenicol , Escherichia coli/drug effects , Escherichia coli/genetics , Escherichia coli/growth & development , Escherichia coli/metabolism , Escherichia coli Infections , Escherichia coli Proteins/genetics , Female , Genes, Bacterial , Mice, Inbred ICR , Plasmids , Reactive Oxygen Species/metabolism
12.
Sci Total Environ ; 810: 152245, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-34896514

ABSTRACT

The rapid dissemination of antibiotic resistance by horizontal gene transfer (HGT) renders the global resistance crisis more tense and urgent as few effective antimicrobials are available to combat multidrug-resistant (MDR) pathogens at present. Conjugation is one of the most dominant and representative pathways of HGT. Antibiotic residue in environment is recognized as an important accelerator for conjugal transfer, whereas the roles of non-antibiotic pharmaceuticals in this process are not fully understood. Here we found that environmentally relevant concentrations of paclitaxel as well as its derivative docetaxel, two commonly used anticancer drugs, remarkably facilitated the conjugative transfer of resistance plasmids carrying multiple antibiotic resistance genes (ARGs). The underlying mechanisms accounting for the enhanced conjugation were investigated by detecting the activity of RpoS regulon, membrane permeability, SOS response and gene expression of conjugative transfer systems. Our results showed that paclitaxel induced a series of cellular responses, including up-regulation of rpoS expression, activated SOS response, increased cell membrane permeability, enhanced plasmid replication and mating pilus formation. Collectively, our data provide new insight on the roles of paclitaxel and its derivative in promoting the conjugal transfer of ARGs, highlighting the importance of good antimicrobial stewardship.


Subject(s)
Anti-Bacterial Agents , Paclitaxel , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Gene Transfer, Horizontal , Genes, Bacterial , Plasmids/genetics
13.
Article in English | MEDLINE | ID: mdl-34682371

ABSTRACT

Based on the customer satisfaction index model, we constructed an elderly care service satisfaction model that includes 5 latent variables and 16 observed variables. To analyze the degree of satisfaction of elderly individuals in nursing homes, we used structural equation model (SEM) to test the nursing service elderly satisfaction model. With the help of AMOS 22.0 software, we analyzed the degree of model fit and the behavioral relationships between the variables that affect the path. We found that the satisfaction of Chinese urban elderly individuals in nursing homes is at a moderate level, which is lower than the quality expected by elderly individuals. The customer satisfaction index model can be applied to assess satisfaction with nursing services. Furthermore, perceived quality and value have a significant impact on satisfaction.


Subject(s)
COVID-19 , Nursing Services , Aged , China/epidemiology , Humans , Pandemics , Personal Satisfaction , SARS-CoV-2
14.
Front Pharmacol ; 12: 673239, 2021.
Article in English | MEDLINE | ID: mdl-34054548

ABSTRACT

The emergence and rapid spread of antibiotic resistance in pathogenic bacteria constitute a global threat for public health. Despite ongoing efforts to confront this crisis, the pace of finding new potent antimicrobials is far slower than the evolution of drug resistance. The abuse of broad-spectrum antibiotics not only accelerates the formation of resistance but also imposes a burden on the intestinal microbiota, which acts a critical role in human homeostasis. As such, innovative therapeutic strategies with precision are pressingly warranted and highly anticipated. Recently, target therapies have achieved some breakthroughs by the aid of modern technology. In this review, we provide an insightful illustration of current and future medical targeted strategies, including narrow-spectrum agents, engineered probiotics, nanotechnology, phage therapy, and CRISPR-Cas9 technology. We discuss the recent advances and potential hurdles of these strategies. Meanwhile, the possibilities to mitigate the spread of resistance in these approaches are also mentioned. Altogether, a better understanding of the advantages, disadvantages, and mechanisms of action of these targeted therapies will be conducive to broadening our horizons and optimizing the existing antibacterial approaches.

15.
Nat Microbiol ; 6(7): 874-884, 2021 07.
Article in English | MEDLINE | ID: mdl-34017107

ABSTRACT

Antibiotic tolerance, the ability of a typically susceptible microorganism to survive extended periods of exposure to antibiotics, has a critical role in chronic and recurrent bacterial infections, and facilitates the evolution of antibiotic resistance. However, the physiological factors that contribute to the development of antibiotic tolerance, particularly in vivo, are not fully known. Despite the fact that a high-fat diet (HFD) is implicated in several human diseases, the relationship between HFD and antibiotic efficacy is still poorly understood. Here, we evaluated the efficacy of multiple clinically relevant bactericidal antibiotics in HFD-fed mice infected with methicillin-resistant Staphylococcus aureus (MRSA) or Escherichia coli. We found that HFD-fed mice had higher bacterial burdens and these bacteria displayed lower susceptibility to bactericidal antibiotic treatment compared with mice that were fed a standard diet, while microbiota-depleted standard-diet- or HFD-fed mice showed similar susceptibility. Faecal microbiota transplantation from HFD-fed mice impaired antibiotic activity in mice fed a standard diet, indicating that alteration of the gut microbiota and related metabolites in HFD-fed mice may account for the decreased antibiotic activity. 16S rRNA sequencing and metabolomics analysis of faecal samples revealed decreased microbial diversity and differential metabolite profiles in HFD-fed mice. Notably, the tryptophan metabolite indole-3-acetic acid (IAA) was significantly decreased in HFD-fed mice. Further in vitro studies showed that IAA supplementation inhibited the formation of bacterial persisters and promoted the elimination of persisters in combination with antibiotic treatment, potentially through the activation of bacterial metabolic pathways. In vivo, the combination of IAA and ciprofloxacin increased the survival rate of HFD-fed mice infected with MRSA persisters. Overall, our data reveal that a HFD has an antagonistic effect on antibiotic treatment in a mouse model, and this is associated with the alteration of the gut microbiota and IAA production.


Subject(s)
Anti-Bacterial Agents/pharmacology , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome/drug effects , Animals , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Bacterial Load/drug effects , Disease Models, Animal , Escherichia coli/drug effects , Escherichia coli/metabolism , Indoleacetic Acids/metabolism , Indoleacetic Acids/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/metabolism , Mice , Obesity/metabolism , Obesity/microbiology
16.
Nat Commun ; 12(1): 2875, 2021 05 17.
Article in English | MEDLINE | ID: mdl-34001908

ABSTRACT

Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Delayed-Action Preparations/administration & dosage , Dexamethasone/administration & dosage , Drug Delivery Systems/methods , Adrenal Cortex Hormones/chemistry , Adrenal Cortex Hormones/pharmacokinetics , Animals , Cells, Cultured , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Dexamethasone/chemistry , Dexamethasone/pharmacokinetics , Dimerization , Disease Models, Animal , Drug Implants , Drug Liberation , Polymers/chemistry , Rabbits , Rats , Uveitis/metabolism , Uveitis/prevention & control
17.
Sci Total Environ ; 773: 145569, 2021 Jun 15.
Article in English | MEDLINE | ID: mdl-33592471

ABSTRACT

Illegal addition of low-dose multi-component residue of hormone-like compounds have sprung up in human activities and production as a cunning strategy to escape from sanitation monitoring, sowing a horrible seed for accidents in food security. Hence, combined strategies with accuracy and efficiency are urgently needed to overcome current circumstance and practical hurdles. Herein, an integrated analysis that compromises recombinant gene yeast bioassay (V400E-YES) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) determination was developed promptly with distinguishing advantage as optimized V400E-YES provides a sum of hormone-like compounds in sample, and subsequent HPLC-MS analysis can accurately quantify the concentration of compounds. In terms of V400E-YES, large-scale random mutagenesis was performed to obtain higher sensitivity hormone receptors. Excitingly, single mutation of estrogen receptor (ER) at V400E and amphimutation of androgen receptor (AR) at G581R/D831E conferred the highest detection sensitivity with a more than 10-fold increase. Subsequently, sensitive HPLC-MS methods for simultaneous detection of eleven estrogens and nine androgens, respectively, were well-constructed. Utilizing this integrated and validated methods, we successfully investigated the hormone residue in environmental samples from farms in Jiangsu, China. Collectively, with multiple estrogens and androgens residue are being widely detected in soil and sewage samples, the feasibility of this method is highlighted, as well as the increasing lurking peril of hormone-like substance residues in environment.


Subject(s)
Biological Assay , Saccharomyces cerevisiae , China , Chromatography, High Pressure Liquid , Estrogens , Humans , Saccharomyces cerevisiae/genetics
18.
Pharmacol Res ; 163: 105276, 2021 01.
Article in English | MEDLINE | ID: mdl-33161137

ABSTRACT

The antibiotic resistance crisis is becoming incredibly thorny due to the indiscriminate employment of antibiotics in agriculture and aquaculture, such as growth promoters, and the emergence of bacteria that are capable of enduring antibiotic treatment in an endless stream. Hence, to reverse this situation, vigorous efforts should be made in the process of identifying other alternative strategies with a lower frequency of resistance. Antimicrobial peptides (AMPs), originated from host defense peptides, are generally produced by a variety of organisms as defensive weapons to protect the host from other pathogenic bacteria. The unique ability of AMPs to control bacterial infections, as well as low propensity to acquire resistance, provides the basis for it to become one of the promising antibacterial substances. Herein, we present new insights into the biological functions, structural properties, distinct mechanisms of action of AMPs and their resistance determinants. Besides, we separately discuss natural and synthetic AMPs, including their source, screening pathway and antibacterial activity. Lastly, challenges and perspectives to identify novel potent AMPs are highlighted, which will expand our understanding of the chemical space of antimicrobials and provide a pipeline for discovering the next-generation of AMPs.


Subject(s)
Drug Resistance, Bacterial , Pore Forming Cytotoxic Proteins , Animals , Humans , Pore Forming Cytotoxic Proteins/chemistry , Pore Forming Cytotoxic Proteins/immunology
19.
Article in English | MEDLINE | ID: mdl-32911826

ABSTRACT

Due to discrimination and media literacy, middle-aged and elderly individuals have been easily reduced to marginalized groups in the identification of rumours during a public health crisis and can easily spread rumours repeatedly, which has a negative impact on pandemic prevention and social psychology. To further clarify the factors influencing their behaviours, this study used a questionnaire to survey a sample of 556 individuals in China and used multiple linear regression and analysis of variance to explore influencing factors during the coronavirus disease 2019 (COVID-19) pandemic. We found that, first, in the COVID-19 pandemic, middle-aged and elderly adults' willingness to re-spread rumours is positively related to their degree of believing rumours and to personal anxiety and is negatively related to their rumour-discrimination ability and to their perception of serious consequences to rumour spreading. Second, the degree of believing rumours plays an intermediary role in the willingness to re-spread rumours. It plays a partial mediating role in the path of anxiety's influence on behaviour, suggesting that an anxious person will spread a rumour even if he or she does not have a strong belief in the rumour. Third, interpersonal communication has a greater credibility and a greater willingness to re-spread than does mass communication. This suggests the importance of increasing public knowledge expertise and of reducing public panic. This also has important implications for the future design of public health policies.


Subject(s)
Anxiety/psychology , Betacoronavirus , Coronavirus Infections/psychology , Deception , Information Dissemination , Pneumonia, Viral/psychology , Aged , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Propaganda , Public Health , SARS-CoV-2
20.
Article in English | MEDLINE | ID: mdl-32823740

ABSTRACT

It is known that the elderly population has weak immune functioning and is a susceptible and high-risk group with respect to the current coronavirus disease 2019 (COVID-19) epidemic. In this study, to understand the influencing factors of COVID-19-related risks and coping behaviors of elderly individuals with respect to COVID-19 and to provide a basis for taking corresponding protective measures, a questionnaire survey was applied to an elderly population. One-way analysis of variance (ANOVA) and linear regression analysis were used to explore the influencing factors of the level of understanding of COVID-19 risks among the elderly population. Additionally, the chi-square test and logistic regression analysis were used to explore the influencing factors of the elderly population's protective behaviors against COVID-19. This study found: (1) The sex, age, and self-care ability of elderly individuals were significantly correlated with their level of understanding of COVID-19, and that those who were female, were of a younger age, or had better self-care ability had higher levels of understanding; (2) The sex, place of residence, and level of understanding of COVID-19 among the elderly individuals were significantly correlated with their protective behaviors, e.g., those who were women, had high levels of understanding, and lived in cities were more likely to have good behaviors; (3) Elderly individuals' assessments of COVID-19 information provided by the government were significantly correlated with their protective behaviors-those who had a positive evaluation of relevant information provided by the government were more likely to develop protective behavior. The conclusions of this study show that it is crucial to implement COVID-19 prevention and control measures in the elderly population. Society, communities, and families need to increase their concerns about the health and risk awareness of the elderly individuals.


Subject(s)
Adaptation, Psychological , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Aged , COVID-19 , Coronavirus Infections/psychology , Coronavirus Infections/virology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/psychology , Pneumonia, Viral/virology , Risk Factors , SARS-CoV-2 , Surveys and Questionnaires
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