ABSTRACT
Mycobacterium marinum(M. marinum ), a slow-growing bacterium in freshwater and seawater, can cause cutanous and extracutaneous infections. A fisher-woman with systemic lupus erythematosus (SLE) presented with chronic polymorphic rashes in a lymphangitic pattern was initially misdiagnosed as sporotrichosis. The final diagnosis of M. marinum and Candida dubliniensis co-infection was confirmed based on the skin histopathology, pustule culture, MetaCAP sequencing and effective antibiotic combination treatments.
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Copper (Cu) is an essential micronutrient for humans, but excessive Cu in rice grains causes health risks. Currently, the mechanisms underlying Cu accumulation in rice are unclear. Here, we identified a novel member of the high-affinity copper transporter (Ctr)-like (COPT) protein family in rice, OsCOPT7, which controls Cu accumulation in rice grains. Mutation in the coding sequence of OsCOPT7 (mutant lc1) leads to inhibition of Cu transport through the xylem, contributing to lower Cu concentrations in the grain of lc1. Knockout or modulation of the expression of OsCOPT7 significantly impacts Cu transportation in the xylem and its accumulation in rice grains. OsCOPT7 localizes at the multi-pass membrane in the cell and the gene is expressed in the exodermis and stele cells, facilitating Cu loading into the xylem. OsCOPT7 expression is upregulated under Cu deficiency and in various organs, implying its contribution to Cu distribution within the rice plant. The variable expression pattern of OsCOPT7 suggests that OsCOPT7 expression responds to Cu stress in rice. Moreover, assays reveal that OsCOPT7 expression level is suppressed by the SQUAMOSA promoter-binding protein-like 9 (OsSPL9) and that OsCOPT7 interacts with Antioxidant Protein1 (OsATX1). This study elucidates the involvement of OsCOPT7 in Cu loading into the xylem, its subsequent distribution within the rice plant, and the potential of this protein in reducing the risk of high Cu concentrations in rice grain grown on Cu-contaminated soil.
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Phytochemical investigation of Gynostemma pentaphyllum led to the purification of five novel dammarane-type triterpene isolates, gypenosides B1 - B5 (1-5). Their structures were determined through comprehensive 1D and 2D NMR spectroscopic analyses and HRESIMS data. Of note, 1-3 are inseparable mixtures of epimers due to their unstable nature, and a total of eight dammarane-type triterpene saponins were identified. Additionally, the protective activities of these new compounds against PC12 cell injury induced by hypoxia were evaluated.
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AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.
Subject(s)
Chlorogenic Acid , Diabetic Nephropathies , Fibrosis , Kidney , Lipid Metabolism , Receptor, Notch1 , STAT3 Transcription Factor , Signal Transduction , STAT3 Transcription Factor/metabolism , Receptor, Notch1/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Animals , Signal Transduction/drug effects , Fibrosis/drug therapy , Chlorogenic Acid/pharmacology , Chlorogenic Acid/therapeutic use , Humans , Mice , Male , Kidney/pathology , Kidney/drug effects , Kidney/metabolism , Lipid Metabolism/drug effects , Molecular Docking Simulation , Mice, Inbred C57BL , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Cell LineABSTRACT
This study aims to explore the effect of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma(LFSMR), a drug pair possesses the function of nourishing Yin, promoting blood circulation, and brightening the eyes, in treating retinitis pigmentosa(RP)by inhibiting the gliosis of Müller cells(MCs) and inducing their reprogramming and differentiation into various types of retinal nerve cells. Twelve C57 mice were used as the normal control group, and 48 transgenic RP(rd10) mice were randomly divided into the model group, positive control group, and low and high dose LFSMR groups, with 12 mice in each group. HE staining was used to detect pathological changes in the retina, and an electroretinogram was used to detect retinal function. Retinal optical coherence tomography was used to detect retinal thickness and perform fundus photography, and laser speckle perfusion imaging was used to detect local retinal blood flow. Digital PCR was used to detect gene expression related to retinal nerve cells, and immunofluorescence was used to detect protein expression related to retinal nerve cells. LFSMR could significantly improve the pathological changes, increase the amplitude of a and b waves, increase the retinal thickness, restore retinal damage, and increase retinal blood flow in mice with RP lesions. LFSMR could also significantly inhibit the m RNA expression of the glial fibrillary acidic protein( GFAP) during the pathogenesis of RP and upregulate m RNA expression of sex determining region Y box protein 2(SOX2), paired box protein 6(Pax6),rhodopsin, protein kinase C-α(PKCα), syntaxin, and thymic cell antigen 1. 1(Thy1. 1). LFSMR could significantly inhibit GFAP protein expression and enhance protein expression of SOX2, Pax6, rhodopsin, PKCα, syntaxin, and Thy1. 1. It could also reverse the pathological changes in the retina of rd10 mice, improve retinal function and fundus performance, increase retinal thickness, enhance local retinal blood flow, and exert therapeutic effects on RP. The mechanism of action of LFSMR may be related to inhibiting the gliosis of MCs and promoting their reprogramming and differentiation into various types of retinal nerve cells.
Subject(s)
Drugs, Chinese Herbal , Ependymoglial Cells , Lycium , Mice, Inbred C57BL , Retinitis Pigmentosa , Salvia miltiorrhiza , Animals , Mice , Ependymoglial Cells/drug effects , Ependymoglial Cells/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Lycium/chemistry , Retinitis Pigmentosa/drug therapy , Retinitis Pigmentosa/genetics , Retinitis Pigmentosa/metabolism , Retinitis Pigmentosa/physiopathology , Salvia miltiorrhiza/chemistry , Male , Retina/drug effects , Rhizome/chemistry , HumansABSTRACT
Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-ß and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.
Subject(s)
Butanones , Hepatic Stellate Cells , Liver Cirrhosis , Mice, Inbred C57BL , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Receptors, Cytoplasmic and Nuclear , Signal Transduction , Animals , Humans , Male , Mice , Butanones/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/drug effects , Inflammation/metabolism , Inflammation/drug therapy , Liver Cirrhosis/metabolism , Liver Cirrhosis/genetics , Liver Cirrhosis/drug therapy , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Rubus/chemistry , Signal Transduction/drug effects , RatsABSTRACT
INTRODUCTION: Phosphodiesterase 9 (PDE9) has been demonstrated as a potential target for neurological disorders and cardiovascular diseases, such as Alzheimer's disease and heart failure. For the last few years, a series of PDE9 inhibitors with structural diversities have been developed and patented by researchers and pharmaceutical companies, providing insights into first-in-class therapies of PDE9 drug candidates. AREA COVERED: This review provides an overview of PDE9 inhibitors in patents from 2018 to the present. EXPERT OPINION: Only a few of the current PDE9 inhibitors are highly selective over other PDEs, which limits their application in pharmacological and clinical research. The design and development of highly selective PDE9 inhibitors remain the top priority in future research. The advantages of targeting PDE9 rather than other PDEs in treating neurodegenerative diseases need to be explained thoroughly. Besides, application of PDE9 inhibitor-based combination therapies sheds light on treating diabetes and refractory heart diseases. Finally, PDE9 inhibitors should be further explored in clinical indications beyond neurological disorders and cardiovascular diseases.
Subject(s)
Cardiovascular Diseases , Drug Development , Patents as Topic , Phosphodiesterase Inhibitors , Humans , Animals , Phosphodiesterase Inhibitors/pharmacology , Cardiovascular Diseases/drug therapy , Drug Design , Nervous System Diseases/drug therapy , 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , 3',5'-Cyclic-AMP Phosphodiesterases/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/physiopathologyABSTRACT
OBJECTIVE: Non-malignant pleural effusions (NMPE) are common in hospitalised patients. Data on NMPE inpatients are scarce and the factors influencing the prognosis are unknown. DESIGN: This was a retrospective cohort study. SETTING AND PARTICIPANTS: We conducted a retrospective cohort of inpatients (n=86 645) admitted to the Chinese PLA General Hospital from 2018 to 2021, based on electronic medical records. The observations of 4934 subjects with effusions confirmed by chest radiological tests (CT or X-ray) without a diagnosis of malignancy were followed during admission. Logistic regression was used to analyse organ damage and other factors associated with in-hospital death. Patients were clustered according to their laboratory indicators, and the association between the clustering results and outcomes was studied. OUTCOME: The outcome of this study was in-hospital mortality. RESULTS: Among 4934 patients, heart failure + pneumonia + renal dysfunction was the most common (15.12%) among 100 different diagnostic groups. 318 (6.4%) patients died during hospitalisation. Lung (OR 3.70, 95% CI 2.42 to 5.89), kidney (OR 2.88, 95% CI 2.14 to 3.90) and heart (1.80, 95% CI 1.29 to 2.55) damage were associated with in-hospital mortality. Hierarchical clustering of laboratory indicators (estimated glomerular filtration rate, white blood cell count, platelet count, haemoglobin, N-terminal pro-B-type natriuretic peptide, serum albumin) demonstrated the ability to discriminate patients at high risk of in-hospital death. CONCLUSION: Comorbidities and multiorgan failure are the prominent characteristics of NMPE patients, which increase the risk of in-hospital mortality, and comprehensive intervention for specific comorbidity patterns is suggested.
Subject(s)
Hospital Mortality , Hospitalization , Pleural Effusion , Humans , Retrospective Studies , Male , Female , Aged , Middle Aged , Prognosis , Hospitalization/statistics & numerical data , China/epidemiology , Risk Factors , Aged, 80 and over , Pneumonia/epidemiology , Pneumonia/mortality , Adult , Heart Failure/mortalitySubject(s)
Osteochondrodysplasias , Humans , Osteochondrodysplasias/complications , Osteochondrodysplasias/diagnostic imaging , Osteochondrodysplasias/diagnosis , Congenital Bone Marrow Failure Syndromes/drug therapy , Congenital Bone Marrow Failure Syndromes/complications , Male , Female , Treatment Outcome , Pancytopenia/etiology , Pancytopenia/drug therapy , Cytopenia , Anemia, RefractoryABSTRACT
Stimuli-responsive physisorbents that undergo reversible structural transformations induced by external stimuli (e.g. light, guests, or heat) offer the promise of utility in gas storage and separation. Whereas reports on guest or light-responsive sorbents have increased in recent years, we are unaware of reports on sorbents that exhibit both light and guest-induced structural transformations. Herein, we report that the square lattice, sql, topology coordination network Zn(fba)(bis) â 2DMF (sql-5,6-Zn-α, 5=trans-4,4'-bis(1-imidazolyl)stilbene=bis, 6=2,2-bis(4-carboxyphenyl)hexafluoropropane=H2fba) underwent single-crystal-to-single-crystal transformation (SCSC) upon activation, affording nonporous sql-5,6-Zn-ß. Parallel alignment at 3.23â Å of olefinic moieties on adjacent bis ligands in sql-5,6-Zn-α enabled SCSC [2+2] photocycloaddition upon exposure to UV light (365â nm) or sunlight. sql-5,6-Zn-α thereby transformed to mot-5,6-Zn-α, which was subsequently activated to the narrow pore phase mot-5,6-Zn-ß. sql-5,6-Zn-ß and mot-5,6-Zn-ß both exhibited S-shaped adsorption isotherms characteristic of guest-induced structural changes when exposed to CO2 at 195â K (type-F-IV and typeâ F-I, respectively). Cycling experiments conducted upon sql-5,6-Zn-ß reduced particle size after cycle 1 and induced transformation into a rare example of a shape memory coordination network, sql-5,6-Zn-γ. Insight into this smorgasbord of SCSC phase changes was gained from in situ PXRD, single crystal XRD and 1H NMR spectroscopy experiments.
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Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species. The present study aims to explore the preventive effect and potential mechanism of DADS on pulmonary fibrosis. C57BL/6J mice were intratracheally injected with bleomycin (BLM) to establish pulmonary fibrosis and then administrated with DADS. Primary lung fibroblasts or A549 were stimulated with BLM, followed by DADS, farnesoid X receptor (FXR) agonist (GW4064), yes-associated protein 1 (YAP1) inhibitor (verteporfin), or silencing of FXR and YAP1. In BLM-stimulated mice, DADS significantly ameliorated histopathological changes and interleukin-1ß levels in bronchoalveolar lavage fluid. DADS decreased fibrosis markers, HIF-1α, inflammatory cytokines, and epithelial-mesenchymal transition in pulmonary mice and activated fibroblasts. DADS significantly enhanced FXR expression and inhibited YAP1 activation, which functions as GW4064 and verteporfin. A deficiency of FXR or YAP1 could result in the increase of these two protein expressions, respectively. DADS ameliorated extracellular matrix deposition, hypoxia, epithelial-mesenchymal transition, and inflammation in FXR or YAP1 knockdown A549. Taken together, targeting the crosstalk of FXR and YAP1 might be the potential mechanism for DADS against pulmonary fibrosis. DADS can serve as a potential candidate or dietary nutraceutical supplement for the treatment of pulmonary fibrosis.
Subject(s)
Allyl Compounds , Disulfides , Mice, Inbred C57BL , Pulmonary Fibrosis , Receptors, Cytoplasmic and Nuclear , Signal Transduction , YAP-Signaling Proteins , Animals , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/chemically induced , Mice , Disulfides/pharmacology , Humans , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction/drug effects , Allyl Compounds/pharmacology , A549 Cells , Male , Allium/chemistry , Adaptor Proteins, Signal Transducing/metabolism , Bleomycin , Lung/drug effects , Lung/pathology , Fibroblasts/drug effects , Fibroblasts/metabolismABSTRACT
A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.
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Fusarium head blight is a devastating disease that causes severe yield loses and mycotoxin contamination in wheat grain. Additionally, balancing the trade-off between wheat production and disease resistance has proved challenging. This study aimed to expand the genetic tools of the endophyte Phomopsis liquidambaris against Fusarium graminearum. Specifically, we engineered a UDP-glucosyltransferase-expressing P. liquidambaris strain (PL-UGT) using ADE1 as a selection marker and obtained a deletion mutant using an inducible promoter that drives Cas9 expression. Our PL-UGT strain converted deoxynivalenol (DON) into DON-3-G in vitro at a rate of 71.4 % after 36 h. DON inactivation can be used to confer tolerance in planta. Wheat seedlings inoculated with endophytic strain PL-UGT showed improved growth compared with those inoculated with wildtype P. liquidambaris. Strain PL-UGT inhibited the growth of Fusarium graminearum and reduced infection rate to 15.7 %. Consistent with this finding, DON levels in wheat grains decreased from 14.25 to 0.56 µg/g when the flowers were pre-inoculated with PL-UGT and then infected with F. graminearum. The expression of UGT in P. liquidambaris was nontoxic and did not inhibit plant growth. Endophytes do not enter the seeds nor induce plant disease, thereby representing a novel approach to fungal disease control.
Subject(s)
Ascomycota , Endophytes , Fusarium , Glucosyltransferases , Plant Diseases , Trichothecenes , Triticum , Triticum/microbiology , Triticum/genetics , Trichothecenes/metabolism , Fusarium/genetics , Fusarium/drug effects , Fusarium/enzymology , Endophytes/genetics , Endophytes/enzymology , Endophytes/metabolism , Plant Diseases/microbiology , Plant Diseases/prevention & control , Glucosyltransferases/genetics , Glucosyltransferases/metabolism , Ascomycota/genetics , Ascomycota/drug effects , Ascomycota/enzymology , Disease Resistance/genetics , Mycotoxins/metabolismABSTRACT
Heart failure is a life-threatening cardiovascular disease and characterized by cardiac hypertrophy, inflammation and fibrosis. The traditional Chinese medicine formula Qiangxinyin (QXY) is effective for the treatment of heart failure while the underlying mechanism is not clear. This study aims to identify the active ingredients of QXY and explore its mechanisms protecting against cardiac hypertrophy. We found that QXY significantly protected against isoproterenol (ISO)-induced cardiac hypertrophy and dysfunction in zebrafish. Eight compounds, including benzoylmesaconine (BMA), atractylenolide I (ATL I), icariin (ICA), quercitrin (QUE), psoralen (PRN), kaempferol (KMP), ferulic acid (FA) and protocatechuic acid (PCA) were identified from QXY. PRN, KMP and icaritin (ICT), an active pharmaceutical ingredient of ICA, prevented ISO-induced cardiac hypertrophy and dysfunction in zebrafish. In H9c2 cardiomyocyte treated with ISO, QXY significantly blocked the calcium influx, reduced intracellular lipid peroxidative product MDA, stimulated ATP production and increased mitochondrial membrane potential. QXY also inhibited ISO-induced cardiomyocyte hypertrophy and cytoskeleton reorganization. Mechanistically, QXY enhanced the phosphorylation of Smad family member 2 (SMAD2) and myosin phosphatase target subunit-1 (MYPT1), and suppressed the phosphorylation of myosin light chain (MLC). In conclusion, PRN, KMP and ICA are the main active ingredients of QXY that protect against ISO-induced cardiac hypertrophy and dysfunction largely via the blockage of calcium influx and inhibition of mitochondrial dysfunction as well as cytoskeleton reorganization.
Subject(s)
Cardiomegaly , Drugs, Chinese Herbal , Isoproterenol , Myocytes, Cardiac , Zebrafish , Animals , Cardiomegaly/chemically induced , Cardiomegaly/drug therapy , Cardiomegaly/prevention & control , Drugs, Chinese Herbal/pharmacology , Myocytes, Cardiac/drug effects , Membrane Potential, Mitochondrial/drug effects , Calcium/metabolism , Rats , Cardiotonic Agents/pharmacology , Cell LineABSTRACT
Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives. Lead 13h exhibited the IC50 of 10 nM against PDE1, high selectivity over other PDEs, as well as good safety properties. Administration of 13h exerted significant anti-liver fibrotic effects in bile duct ligation-induced fibrosis rats, which also prevented TGF-ß-induced myofibroblast differentiation in vitro, confirming that PDE1 could work as a potential target for liver fibrosis.
Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 1 , Drug Design , Liver Cirrhosis , Phosphodiesterase Inhibitors , Pyrimidines , Animals , Cyclic Nucleotide Phosphodiesterases, Type 1/antagonists & inhibitors , Cyclic Nucleotide Phosphodiesterases, Type 1/metabolism , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Pyrimidines/chemistry , Pyrimidines/therapeutic use , Humans , Rats , Phosphodiesterase Inhibitors/pharmacology , Phosphodiesterase Inhibitors/chemical synthesis , Phosphodiesterase Inhibitors/therapeutic use , Phosphodiesterase Inhibitors/chemistry , Male , Structure-Activity Relationship , Rats, Sprague-Dawley , Molecular Docking Simulation , Molecular StructureABSTRACT
As essential primary producers, cyanobacteria play a major role in global carbon and nitrogen cycles. Though the influence of nanoplastics on the carbon metabolism of cyanobacteria is well-studied, little is known about how nanoplastics affect their nitrogen metabolism, especially under environmentally relevant nitrogen concentrations. Here, we show that nitrogen forms regulated growth inhibition, nitrogen consumption, and the synthesis and release of microcystin (MC) in Microcystis aeruginosa exposed to 10 µg/mL amino-modified polystyrene nanoplastics (PS-NH2) with a particle size of 50 nm under environmentally relevant nitrogen concentrations of nitrate, ammonium, and urea. We demonstrate that PS-NH2 inhibit M. aeruginosa differently in nitrate, urea, and ammonium, with inhibition rates of 51.87, 39.70, and 36.69%, respectively. It is caused through the differences in impairing cell membrane integrity, disrupting redox homeostasis, and varying nitrogen transport pathways under different nitrogen forms. M. aeruginosa respond to exposure of PS-NH2 by utilizing additional nitrogen to boost the production of amino acids, thereby enhancing the synthesis of MC, extracellular polymeric substances, and membrane phospholipids. Our results found that the threat of nanoplastics on primary producers can be regulated by the nitrogen forms in freshwater ecosystems, contributing to a better understanding of nanoplastic risks under environmentally relevant conditions.
Subject(s)
Microcystis , Nitrogen , Microcystis/drug effects , Microcystis/metabolism , Microcystis/growth & development , Nitrogen/chemistry , Nitrogen/metabolism , Microcystins/metabolism , Polystyrenes/chemistry , Particle Size , Microplastics/metabolism , Nanoparticles/chemistry , Nitrates/metabolism , Nitrates/chemistry , Urea/metabolism , Urea/chemistry , Urea/pharmacologyABSTRACT
With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. Mycobacterium marinum, as a model organism of Mycobacterium tuberculosis, can be used for the rapid and efficient screening of bioactive compounds. The 14-membered resorcylic acid lactones (RALs) have a wide range of bioactivities such as antibacterial, antifouling and antimalarial activity. In order to further study their bioactivities, we initially constructed a 14-membered RALs library, which contains 16 new derivatives. The anti-M. marinum activity was evaluated in vitro. Derivatives 12, 19, 20 and 22 exhibited promising activity with MIC90 values of 80, 90, 80 and 80 µM, respectively. The preliminary structure-activity relationships showed that the presence of a chlorine atom at C-5 was a key factor to improve activity. Further studies showed that 12 markedly inhibited the survival of M. marinum and significantly reduced the dosage of positive drugs isoniazid and rifampicin when combined with them. These results suggest that 12 is a bioactive compound capable of enhancing the potency of existing positive drugs, and its effective properties make it a very useful leads for future drug development in combating TB resistance.
Subject(s)
Antimalarials , Mycobacterium marinum , Antibodies , Antitubercular Agents , LactonesABSTRACT
AIM: To synthesise evidence from the literature on hospital nurses' perceived challenges and opportunities in the care of people with dementia. BACKGROUND: People with dementia often have longer lengths of hospital stay and poorer health outcomes compared to those without dementia. Nurses play a pivotal role in the care of people with dementia. However, there is a scarcity of systematic reviews that synthesise the challenges and opportunities they perceive. METHODS: A mixed-methods systematic review was conducted with a database search covering Ageline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Emcare, Embase, Medline, PsycINFO, ProQuest, Scopus and Web of Science in April 2022. In total, 27 articles that met the selection criteria were critically reviewed and included in this systematic review. Data from the selected articles were extracted and synthesised using a convergent segregated approach. RESULTS: Three main themes and eight subthemes were identified. Theme 1 described nurse-related factors consisting of the lack of capability in dementia care, experiencing multiple sources of stress and opportunities for nurses to improve dementia care. Theme 2 revealed people living with dementia-related factors including complex care needs and the need to engage family carers in care. Theme 3 explained organisation-related factors comprising the lack of organisational support for nurses and people with dementia and opportunities for quality dementia care. CONCLUSION: Hospital nurses experience multidimensional challenges in the care of people with dementia. Opportunities to overcome those challenges include organisational support for nurses to develop dementia care capability, reduce their stress and partner with the family caregivers. RELEVANCE TO CLINICAL PRACTICE: Hospitals will need to build an enabling environment for nurses to develop their capabilities in the care of people with dementia. Further research in empowering nurses and facilitating quality dementia care in acute care hospitals is needed. REPORTING METHOD: The review followed the PRISMA 2020 checklist. PATIENT OR PUBLIC CONTRIBUTION: No.
Subject(s)
Dementia , Nursing Staff, Hospital , Humans , Dementia/nursing , Nursing Staff, Hospital/psychology , Attitude of Health Personnel , FemaleABSTRACT
BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.
Subject(s)
2019-nCoV Vaccine mRNA-1273 , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , HIV Infections , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , Male , Female , COVID-19/prevention & control , COVID-19/immunology , Antibodies, Viral/blood , Middle Aged , HIV Infections/immunology , Spike Glycoprotein, Coronavirus/immunology , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/immunology , SARS-CoV-2/immunology , Immunoglobulin G/blood , Adult , 2019-nCoV Vaccine mRNA-1273/immunology , 2019-nCoV Vaccine mRNA-1273/administration & dosage , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Vaccination/methods , Vaccine Efficacy , SeroconversionABSTRACT
Inverted colloidal-nanocrystal-based LEDs (NC-LEDs) are highly interesting and invaluable for large-scale display technology and flexible electronics. Semiconductor nanorods (NRs), in addition to the tunable wavelengths of the emitted light (achieved, for example, by the variation of the NR diameter or the diameter of core in a core-shell configuration), also exhibit linearly polarized emission, a larger Stokes shift, faster radiative decay, and slower bleaching kinetics than quantum dots (QDs). Despite these advantages, it is difficult to achieve void-free active NR layers using simple spin-coating techniques. Herein, we employ electrophoretic deposition (EPD) to make closely packed, vertically aligned CdSe/CdS core/shell nanorods (NRs) as the emissive layer. Following an inverted architecture, the device fabricated yields an external quantum efficiency (EQE) of 6.3% and a maximum luminance of 4320 cd/m2 at 11 V. This good performance can be attributed to the vertically aligned NR layer, enhancing the charge transport by reducing the resistance of carrier passage, which is supported by our finite element simulations. To the best of our knowledge, this is the first time vertically aligned NR layers made by EPD have been reported for the fabrication of NC-LEDs and the device performance is one of the best for inverted red NR-LEDs. The findings presented in this work bring forth a simple and effective technique for making vertically aligned NRs, and the mechanism behind the NR-LED device with enhanced performance using these NRs is illustrated. This technique may prove useful to the development of a vast class of nanocrystal-based optoelectronics, including solar cells and laser devices.