ABSTRACT
Genetically encoded voltage indicators are emerging tools for monitoring voltage dynamics with cell-type specificity. However, current indicators enable a narrow range of applications due to poor performance under two-photon microscopy, a method of choice for deep-tissue recording. To improve indicators, we developed a multiparameter high-throughput platform to optimize voltage indicators for two-photon microscopy. Using this system, we identified JEDI-2P, an indicator that is faster, brighter, and more sensitive and photostable than its predecessors. We demonstrate that JEDI-2P can report light-evoked responses in axonal termini of Drosophila interneurons and the dendrites and somata of amacrine cells of isolated mouse retina. JEDI-2P can also optically record the voltage dynamics of individual cortical neurons in awake behaving mice for more than 30 min using both resonant-scanning and ULoVE random-access microscopy. Finally, ULoVE recording of JEDI-2P can robustly detect spikes at depths exceeding 400 µm and report voltage correlations in pairs of neurons.
Subject(s)
Microscopy , Neurons , Animals , Interneurons , Mice , Microscopy/methods , Neurons/physiology , Photons , WakefulnessABSTRACT
To increase computational flexibility, the processing of sensory inputs changes with behavioural context. In the visual system, active behavioural states characterized by motor activity and pupil dilation1,2 enhance sensory responses, but typically leave the preferred stimuli of neurons unchanged2-9. Here we find that behavioural state also modulates stimulus selectivity in the mouse visual cortex in the context of coloured natural scenes. Using population imaging in behaving mice, pharmacology and deep neural network modelling, we identified a rapid shift in colour selectivity towards ultraviolet stimuli during an active behavioural state. This was exclusively caused by state-dependent pupil dilation, which resulted in a dynamic switch from rod to cone photoreceptors, thereby extending their role beyond night and day vision. The change in tuning facilitated the decoding of ethological stimuli, such as aerial predators against the twilight sky10. For decades, studies in neuroscience and cognitive science have used pupil dilation as an indirect measure of brain state. Our data suggest that, in addition, state-dependent pupil dilation itself tunes visual representations to behavioural demands by differentially recruiting rods and cones on fast timescales.
Subject(s)
Color , Pupil , Reflex, Pupillary , Vision, Ocular , Visual Cortex , Animals , Darkness , Deep Learning , Mice , Photic Stimulation , Pupil/physiology , Pupil/radiation effects , Reflex, Pupillary/physiology , Retinal Cone Photoreceptor Cells/drug effects , Retinal Cone Photoreceptor Cells/physiology , Retinal Rod Photoreceptor Cells/drug effects , Retinal Rod Photoreceptor Cells/physiology , Time Factors , Ultraviolet Rays , Vision, Ocular/physiology , Visual Cortex/physiologyABSTRACT
SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.
Subject(s)
COVID-19 , Severe acute respiratory syndrome-related coronavirus , Humans , Severe acute respiratory syndrome-related coronavirus/genetics , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Proteolysis , Virus Replication , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolismABSTRACT
It has been documented that caspase 3 activity is necessary for skeletal muscle regeneration, but how its activity is regulated is largely unknown. Our previous report shows that intracellular TMEM16A, a calcium activated chloride channel, significantly regulates caspase 3 activity in myoblasts during skeletal muscle development. By using a mouse line with satellite cell (SC)-specific deletion of TMEM16A, we examined the role of TMEM16A in regulating caspase 3 activity in SC (or SC-derived myoblast) as well as skeletal muscle regeneration. The mutant animals displayed apparently impaired regeneration capacity in adult muscle along with enhanced ER stress and elevated caspase 3 activity in Tmem16a-/- SC derived myoblasts. Blockade of either excessive ER stress or caspase 3 activity by small molecules significantly restored the inhibited myogenic differentiation of Tmem16a-/- SCs, indicating that excessive caspase 3 activity resulted from TMEM16A deletion contributes to the impaired muscle regeneration and the upstream regulator of caspase 3 was ER stress. Our results revealed an essential role of TMEM16A in satellite cell mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.
ABSTRACT
Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4â³-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+⢠radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-Bâ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.
Subject(s)
Phototherapy , Photothermal Therapy , Hydrogels/pharmacologyABSTRACT
Crustaceans have an open vascular system in which hemocytes freely circulate in hemolymph. Hemocytes are rich in hemocyanin, a specific oxygen-transport protein in crustaceans; therefore, understanding the response of hemocytes to hypoxia is crucial. Although hemocytes take up glucose during hypoxia, the molecular mechanism of glucose uptake in crustaceans remains unclear. Herein, we identified two highly conserved glucose transporters (GLUT1 and GLUT2) in Macrobrachium nipponense (oriental river prawn) and analyzed their tissue-specific expression patterns. Our immunofluorescence assays showed that GLUT1 and GLUT2 are located on the cell membrane, with a strong GLUT1 signal in primary hemocytes under hypoxia. We found that during acute hypoxia, hypoxia-inducible factor-1α-related metabolic alterations result in decreased mitochondrial cytochrome c oxidase activity, implying a classic glycolytic mechanism. As a proof of concept, we replicated these findings in insect S2 cells. Acute hypoxia significantly induced hypoxia-inducible factor-1α, GLUT1, and pyruvate dehydrogenase kinase isozyme 1 expression in primary hemocytes, and hypoxia-induced increases in glucose uptake and lactate secretion were observed. GLUT1 knockdown induced intracellular reactive oxygen species generation and apoptosis in vitro and in vivo, resulting in increased prawn mortality and more apoptotic cells in their brains, implying a vital function of GLUT1 in hypoxia adaptation. Taken together, our results suggest a close relationship between hypoxia-mediated glycolysis and GLUT1 in hemocytes. These results demonstrated that in crustaceans, adaptation to hypoxia involves glucose metabolic plasticity.
Subject(s)
Palaemonidae , Animals , Palaemonidae/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Glucose Transport Proteins, Facilitative/metabolism , Glucose Transporter Type 1/genetics , Glucose Transporter Type 1/metabolism , Hemocytes/metabolism , Gene Expression Regulation , Hypoxia/metabolism , Glucose/metabolismABSTRACT
The 70 kD heat shock proteins (HSP70s) represent a class of molecular chaperones that are widely distributed in all kingdoms of life, which play important biological roles in plant growth, development, and stress resistance. However, this family has not been systematically characterized in radish (Raphanus sativus L.). In this study, we identified 34 RsHSP70 genes unevenly distributed within nine chromosomes of R. sativus. Phylogenetic and multiple sequence alignment analyses classified the RsHSP70 proteins into six distinct groups (Group A-F). The characteristics of gene structures, motif distributions, and corresponding cellular compartments were more similar in closely linked groups. Duplication analysis revealed that segmental duplication was the major driving force for the expansion of RsHSP70s in radish, particularly in Group C. Synteny analysis identified eight paralogs (Rs-Rs) in the radish genome and 19 orthologs (Rs-At) between radish and Arabidopsis, and 23 orthologs (Rs-Br) between radish and Chinese cabbage. RNA-seq analysis showed that the expression change of some RsHSP70s were related to responses to heat, drought, cadmium, chilling, and salt stresses and Plasmodiophora brassicae infection, and the expression patterns of these RsHSP70s were significantly different among 14 tissues. Furthermore, we targeted a candidate gene, RsHSP70-23, the product of which is localized in the cytoplasm and involved in the responses to certain abiotic stresses and P. brassicae infection. These findings provide a reference for further molecular studies to improve yield and stress tolerance of radish.
Subject(s)
Arabidopsis , Raphanus , Raphanus/genetics , Raphanus/metabolism , Phylogeny , HSP70 Heat-Shock Proteins/genetics , HSP70 Heat-Shock Proteins/metabolism , Synteny , Stress, Physiological/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Genome, PlantABSTRACT
Halophyte-based remediation emerges as a novel strategy for ameliorating saline soils, offering a sustainable alternative to conventional leaching methods. While bioremediation is recognized for its ability to energize soil fertility and structure, the complex interplays among plant traits, soil functions, and soil microbial diversity remain greatly unknown. Here, we conducted a 5-year field experiment involving the continuous cultivation of the annual halophyte Suaeda salsa in saline soils to explore soil microbial diversity and their relationships with plant traits and soil functions. Our findings demonstrate that a decline in soil salinity corresponded with increases in the biomass and seed yield of S. salsa, which sustained a consistent seed oil content of approximately 22% across various salinity levels. Significantly, prolonged cultivation of halophytes substantially augmented soil microbial diversity, particularly from the third year of cultivation. Moreover, we identified positive associations between soil multifunctionality, seed yield, and taxonomic richness within a pivotal microbial network module. Soils enriched with taxa from this module showed enhanced multifunctionality and greater seed yields, correlating with the presence of functional genes implicated in nitrogen fixation and nitrification. Genomic analysis suggests that these taxa have elevated gene copy numbers of crucial functional genes related to nutrient cycling. Overall, our study emphasizes that the continuous cultivation of S. salsa enhances soil microbial diversity and recovers soil multifunctionality, expanding the understanding of plant-soil-microbe feedback in bioremediation.IMPORTANCEThe restoration of saline soils utilizing euhalophytes offers a viable alternative to conventional irrigation techniques for salt abatement and soil quality enhancement. The ongoing cultivation of the annual Suaeda salsa and its associated plant traits, soil microbial diversity, and functionalities are, however, largely underexplored. Our investigation sheds light on these dynamics, revealing that cultivation of S. salsa sustains robust plant productivity while fostering soil microbial diversity and multifunctionality. Notably, the links between enhanced soil multifunctionality, increased seed yield, and network-dependent taxa were found, emphasizing the importance of key microbial taxa linked with functional genes vital to nitrogen fixation and nitrification. These findings introduce a novel understanding of the role of soil microbes in bioremediation and advance our knowledge of the ecological processes that are vital for the rehabilitation of saline environments.
Subject(s)
Chenopodiaceae , Soil , Soil/chemistry , Saline Solution , Sodium Chloride , Nitrification , Salt-Tolerant PlantsABSTRACT
Retinopathy of prematurity (ROP) is the leading cause of blindness in children, but there is no safe and effective treatment available. Interleukin-1 receptor type 2 (IL1R2) acts as a decoy receptor for IL-1 may affect ROP progression. This study aimed to investigate the role of IL1R2 in ROP. A microglial cell model was established under hypoxia conditions and co-cultured with choroidal endothelial cells, while an oxygen-induced retinopathy (OIR) model was also established. Microglial activation and IL1R2 levels in retinal tissues were analyzed using immunofluorescence assay. Endothelial cell migration was evaluated by Transwell assay and scratch test, angiogenesis was assessed using ELISA and tube formation assay, and proliferation was evaluated by EdU assay. The HIF1α/PFKFB3 pathway was analyzed by western blot. We observed that IL1R2 expression was predicted to be upregulated in ROP and was increased in hypoxia-treated BV2 cells. Additionally, IL1R2 levels were upregulated in the retinal tissues of OIR mice and correlated with microglial activation. In vitro experiments, we found that hypoxia promoted endothelial cell migration, angiogenesis, proliferation, and activated the HIF1α/PFKFB3 pathway, which were rescued by IL1R2 knockdown. Moreover, NHWD-870 (a HIF1α/PFKFB3 pathway inhibitor) suppressed endothelial cell migration, angiogenesis, and proliferation induced by IL1R2 overexpression. In conclusion, IL1R2 facilitates the migration, angiogenesis, and proliferation of choroidal endothelial cells by activating the HIF1α/PFKFB3 pathway to regulate ROP progression.
Subject(s)
Retinal Neovascularization , Retinopathy of Prematurity , Animals , Humans , Mice , Angiogenesis , Disease Models, Animal , Endothelial Cells/metabolism , Hypoxia/metabolism , Mice, Inbred C57BL , Oxygen/metabolism , Phosphofructokinase-2/adverse effects , Phosphofructokinase-2/metabolism , Receptors, Interleukin-1 Type II/metabolism , Retina/metabolism , Retinal Neovascularization/metabolism , Retinopathy of Prematurity/metabolismABSTRACT
Optically transparent glass with antifogging and antibacterial properties is in high demand for endoscopes, goggles, and medical display equipment. However, many of the previously reported coatings have limitations in terms of long-term antifogging and efficient antibacterial properties, environmental friendliness, and versatility. In this study, inspired by catfish and sphagnum moss, a novel photoelectronic synergy antifogging and antibacterial coating was prepared by cross-linking polyethylenimine-modified titanium dioxide (PEI-TiO2), polyvinylpyrrolidone (PVP), and poly(acrylic acid) (PAA). The as-prepared coating could remain fog-free under hot steam for more than 40 min. The experimental results indicate that the long-term antifogging properties are due to the water absorption and spreading characteristics. Moreover, the organic-inorganic hybrid of PEI and TiO2 was first applied to enhance the antibacterial performance. The Staphylococcus aureus and the Escherichia coli growth inhibition rates of the as-prepared coating reached 97 and 96% respectively. A photoelectronic synergy antifogging and antibacterial mechanism based on the positive electrical and photocatalytic properties of PEI-TiO2 was proposed. This investigation provides insight into designing multifunctional bioinspired surface materials to realize antifogging and antibacterial that can be applied to medicine and daily lives.
Subject(s)
Anti-Bacterial Agents , Escherichia coli , Staphylococcus aureus , Titanium , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Titanium/chemistry , Titanium/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacology , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Microbial Sensitivity Tests , Povidone/chemistry , Surface PropertiesABSTRACT
Molecularly imprinted polymer (MIP)-based chromatographic separation materials, owing to their advantages of unique selectivity, low cost, suitable reproducibility, and acceptable stability, have attracted a great deal of research in different fields. In this investigation, a new type of MIP-coated silica (MIP/SiO2) separation material was developed using sulfamethoxazole as a template; the specific recognition ability of MIP and appropriate physicochemical properties (abundant Si-OH, suitable pore structure, good stability, etc.) of SiO2 microbeads were combined. The MIP/SiO2 separation materials were characterized carefully. Then, various compounds (such as sulfonamides, ginsenosides, nucleosides, and several pesticides) were used to comprehensively evaluate the chromatographic performances of the MIP/SiO2 column. Furthermore, the chromatographic performances of the MIP/SiO2 column were compared with those of other separation materials (such as non-imprinted polymer-coated silica, C18/SiO2, and bare silica) packed columns. The resolution value of all measured compounds was more than 1.51. The column efficiencies of 13 510 plates per meter (N m-1) for sulfamethoxazole, 11 600 N m-1 for ginsenoside Rd, and 10 510 N m-1 for 2'-deoxyadenosine were obtained. The acceptable results verified that the MIP/SiO2 column can be applied to separate highly polar drugs such as sulfonamides, ginsenosides, nucleosides, and pesticides.
Subject(s)
Microspheres , Molecularly Imprinted Polymers , Silicon Dioxide , Silicon Dioxide/chemistry , Chromatography, High Pressure Liquid/methods , Molecularly Imprinted Polymers/chemistry , Ginsenosides/chemistry , Ginsenosides/analysis , Ginsenosides/isolation & purification , Molecular Imprinting/methods , Nucleosides/chemistry , Nucleosides/isolation & purification , Nucleosides/analysis , Pesticides/analysis , Pesticides/chemistry , Pesticides/isolation & purification , Polymers/chemistryABSTRACT
OBJECTIVE: The accessibility issue of orphan drugs in China is prominent. Based on real-world data from a tier-one city in Northeast China, this study aims to analyze the current usage and affordability of orphan drugs for rare diseases. METHODS: The data was sourced from the health insurance claims data of a certain city from 2018 to 2021, including a total of 16 orphan drugs. The utilization of orphan drugs is assessed using four indicators: frequency of medical insurance claims, medication cost, defined daily doses (DDDs), and defined daily drug cost (DDDc). Affordability is measured using the concept of catastrophic health expenditure (CHE). RESULTS: Between January 2018 and December 2021, there were a total of 2,851 medical insurance claims in the city, with a total medication costs of $3.08 million. Overall, during the study, there was a year-on-year increase in the utilization frequency of individual rare disease drugs in the city, with DDDs rising from 140.22 in 2018 to 3983.63 in 2021. Additionally, the annual medication costs of individual drugs showed a consistent upward trend, increasing from $10,953.53 in 2018 to $120,491.36 in 2021. However, the DDDc of individual drugs decreased from $398.12 in 2018 to $96.65 in 2021.The number of sales and the amount of sales for orphan drugs in community pharmacies have significantly increased. Prior to medical insurance coverage, out of the 16 orphan drugs, 9 drugs had annual treatment costs exceeding CHE for urban residents, and 15 drugs had annual treatment costs exceeding CHE for rural residents. After medical insurance coverage, there were no drugs with out-of-pocket costs exceeding CHE for urban residents, while 8 drugs had out-of-pocket costs exceeding CHE for rural residents. Furthermore, both before and after medical insurance coverage, the four treatment drugs for idiopathic pulmonary arterial hypertension were more affordable compared to the four treatment drugs for multiple sclerosis. CONCLUSION: The usage frequency of orphan drugs in a certain city increased gradually, but the disease burden remained heavy. More policy support should be provided to the priority rare disease populations, and the rare disease medical security and diagnosis and treatment systems should be improved.
Subject(s)
Insurance Coverage , Insurance, Health , Orphan Drug Production , Rare Diseases , Humans , China , Rare Diseases/drug therapy , Orphan Drug Production/economics , Orphan Drug Production/statistics & numerical data , Insurance Coverage/statistics & numerical data , Insurance, Health/statistics & numerical data , Drug Costs/trends , Health Expenditures/statistics & numerical data , Databases, Factual , Health Services Accessibility/statistics & numerical dataABSTRACT
Studies have shown that protein phosphorylation plays an important role in morphine abuse. However, the neurobiological mechanism of protein phosphatase 2A (PP2A) underlying the morphine-priming process is still unclear. Here we constructed T29-2-Cre; PP2Afl/fl conditional knockout mice (KO) and investigated the role of hippocampal PP2A in morphine priming. We observed that the deficit of PP2A inhibited the priming behavior of morphine and blocked the priming-induced long-term potentiation (LTP) in the hippocampus of KO mice. Moreover, the expression levels of Rack1 and the membrane GluN2B were significantly reduced in the nucleus accumbens of KO mice compared with those in the control mice, which may be attributed to the decreased HDAC4 in the hippocampus of KO mice. Consistent with it, the similar inhibited priming effects were also observed in the wild-type mice treated with sodium butyrate (NaB)-a nonspecific inhibitor of histone deacetylases-3 h after morphine administration. Taken together, our results suggest that hippocampal PP2A may be involved in morphine priming through the PP2A/HDAC4/Rack1 pathway.
Subject(s)
Morphine , Protein Phosphatase 2 , Mice , Animals , Morphine/pharmacology , Morphine/metabolism , Protein Phosphatase 2/metabolism , Hippocampus/metabolism , Long-Term Potentiation , Mice, KnockoutABSTRACT
This study aims to explore the molecular mechanisms and associated pathways of myocardial infarction (MI). We employed a variety of analytical methods, including Mendelian Randomization (MR) analysis, transcriptome microarray data analysis, gene function and pathway enrichment analysis, untargeted metabolomic mass spectrometry analysis, and gene-metabolite interaction network analysis. The MR analysis results revealed a significant impact of mitochondrial DNA copy number on MI and coronary artery bypass grafting. Transcriptome analysis unveiled numerous differentially expressed genes associated with myocardial ischemia, with enrichment observed in cardiac function and energy metabolism pathways. Metabolomic analysis indicated a significant downregulation of mitochondrial regulation pathways in ischemic myocardium. T500 metabolite quantification analysis identified 90 differential metabolites between MI and Sham groups, emphasizing changes in metabolites associated with energy metabolism. Gene-metabolite interaction network analysis revealed the significant roles of key regulatory molecules such as HIF1A, adenosine, TBK1, ATP, NRAS, and EIF2AK3, in the pathogenesis of myocardial ischemia. In summary, this study provides important insights into the molecular mechanisms of MI and highlights interactions at multiple molecular levels, contributing to the establishment of new theoretical foundations for the diagnosis and treatment of MI.
Subject(s)
Adenosine , Myocardial Infarction , Myocardial Infarction/metabolism , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Humans , Adenosine/metabolism , Energy Metabolism/genetics , Gene Regulatory Networks , Gene Expression Profiling , Mendelian Randomization Analysis , DNA, Mitochondrial/genetics , Mitochondria/metabolism , Metabolomics/methods , TranscriptomeABSTRACT
BACKGROUND: The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China. METHODS: We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region. RESULTS: During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients' payment capability level, but an increasing trend (11.94%-18.42) under rural patients' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend. CONCLUSION: This study demonstrates that access to drugs for urban cancer patients has improved. However, patients' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation's health insurance funds.
Subject(s)
Antineoplastic Agents , Drug Costs , Insurance, Health , Humans , China , Antineoplastic Agents/economics , Antineoplastic Agents/therapeutic use , Drug Costs/statistics & numerical data , Insurance, Health/economics , Insurance, Health/statistics & numerical data , Neoplasms/drug therapy , Neoplasms/economics , Female , Male , Negotiating , Health Expenditures/statistics & numerical data , Middle AgedABSTRACT
AIMS: To comprehensively examine the prevailing condition of care dependence among middle-aged individuals who have experienced hemiplegia subsequent to a stroke and were currently undergoing post-acute rehabilitation. Additionally, the study sought to analyse the determinants that impacted this phenomenon. DESIGN: A single-centre, cross-sectional study design. METHODS: During the period from January 2020 to October 2022, a cohort of 196 hemiplegic stroke patients, aged between 40 and 65, and within 6 months of their stroke onset, was selected from the cerebrovascular outpatient clinic at a tertiary hospital in Hangzhou. The demographic and disease-related data, care dependence level, mental state, nutrition and depression status were collected. Furthermore, all collected data were analysed by descriptive and correlative statistical methods. RESULTS: The care dependence level was 51.04 ± 9.42, with an incidence of care dependence of 78.1%. Multivariate regression analysis showed that age, history of falls, physical dysfunction, chronic comorbidities, depression, nutritional status and cognitive dysfunction were influencing factors for care dependence in the participants after a stroke. CONCLUSION: The incidence of care dependence among hemiplegic patients aged from 40 to 65 years old in the early stage after a stroke was high. Nursing staff should focus on these patients with a history of falling, physical dysfunction, comorbidity, depression status, nutritional status and cognitive dysfunction in clinical practice. RELEVANCE TO CLINICAL PRACTICE: The incidence of care dependence in middle-aged hemiplegic patients following a stroke is significantly increased. Some risk factors should be assessed, monitored, and controlled by nursing staff as early as possible in order to reduce the dependence levels in post-acute rehabilitation period and improve the quality of life of hemiplegia patients. REPORTING METHOD: Our study complies with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist: cross-sectional studies (see Table S1). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
Subject(s)
Hemiplegia , Stroke Rehabilitation , Stroke , Humans , Middle Aged , Male , Female , Cross-Sectional Studies , Aged , Stroke Rehabilitation/methods , Stroke Rehabilitation/statistics & numerical data , Stroke/complications , Stroke/nursing , Adult , China/epidemiologyABSTRACT
One promising approach to overcome drug resistance in asthma treatments involves dual-target therapy, specifically targeting the ß2 adrenergic receptor (ß2-AR) and muscarinic-3 acetylcholine receptor (M3R). This study investigated the anti-asthma effects and dual-target mechanisms of glycyrrhizic acid, hesperidin, and platycodin D (GHP) from Zhisou San. GHP administration effectively attenuated OVA-induced inflammatory infiltration and overproduction of mucus in asthmatic mice. Additionally, GHP treatment significantly suppressed M3R and promoted ß2-AR activation, resulting in the relaxation of tracheal smooth muscle. These findings concluded that GHP mitigated asthma by targeting ß2-AR and M3R to ameliorate airway inflammation and modulate airway smooth muscle relaxation.
ABSTRACT
Biochar preparation and application is an anticipated pathway for the resource utilization of biogas residue. In this study, biochars were prepared by the pyrolysis of biogas residue from food waste anaerobic digestion (named as BRBCs) under various pyrolysis temperatures (300, 500, 700, and 900 °C), and the effect of pyrolysis temperatures on the physicochemical characteristics of BRBCs was examined. The adsorption performance toward ciprofloxacin (CIP), a typical antibiotic in waterbodies, was also investigated. The results showed that pyrolysis temperature significantly changed the physicochemical properties of BRBCs. In addition, the minerals in the biogas residue, especially SiO2, were rearranged to form a mesoporous structure in biochar through a self-template strategy (without activator). BRBC prepared at 900 °C exhibited a high specific surface area and pore volume, well-developed mesopore structure, and more carbon structure defects, and exhibited the largest CIP adsorption capacity with 70.29 mg g-1, which was ascribed to the combined interaction of pore diffusion, π-π interactions, hydrogen bonding, complexation, and electrostatic forces. Furthermore, the adsorption of CIP by BRBC900 was well described by two-compartment kinetic and Langmuir isotherm models. BRBC900 showed good adsorption performance toward CIP at pH 7-9. The adsorption of CIP by BRBC is a spontaneous, exothermic, entropy-increasing process. Moreover, BRBC also presented a good recycling potential. Therefore, the preparation of mesoporous biochar based on a self-template strategy not only provides an option for the resource utilization of biogas residue but also offers a new option for the treatment of antibiotic wastewater.
Subject(s)
Biofuels , Charcoal , Ciprofloxacin , Pyrolysis , Ciprofloxacin/chemistry , Charcoal/chemistry , Biofuels/analysis , Adsorption , Water Pollutants, Chemical/chemistry , Temperature , Porosity , KineticsABSTRACT
BACKGROUND: Root canal therapy is one of the main treatments for root canal diseases, and effective irrigation is the key to successful treatment. Side-vented needle is one of the commonly used needle types in clinic. In the real root canal, due to the influence of the curvature of the root canal, the irrigation flow field in different needle directions shows obvious differences. At the same time, changes in root canal curvature and working depth will lead to changes in irrigation efficiency and the flow field. Both the mainstream of the irrigation flow and the shear stress near the wall changes significant. Consequently, either the replacement in the root canal or the removal efficiency of the smear layers is apparently modified. MATERIALS AND METHODS: In this paper, the permanent root canal of the maxillary first molar prepared until 15/04 were scanned by micro-CT, and then imported into the software for 3D reconstruction. The key parameters of flushing efficiency of 30G side needle at different working depths of 4.75 mm, 5 mm, 5.25 mm and 5.5 mm were compared. Meanwhile, the simulated models with different curvatures of 0°, 5°, 10°, 20° and 30° based on the real root canal were reconstructed to investigate the curvature effect on the irrigation efficiency. RESULTS: The results show that moderate working depth (such as 4.75 mm and 5.25 mm in present paper) helps to improve the replacement capacity of irrigation flow. At the same time, the apical pressure decreased as the working depth increased. The curvature of the root canal seriously affects the removal depth of the smear layers of the root canal. A root canal with a large curvature (especially 20° and 30°) can significantly improve the difficulty of irrigation. CONCLUSIONS: (1) Moderate working depth helps to improve the displacement capacity, the ERD of the irrigation flow is generally improved at the working depths of 4.75 mm and 5.25 mm, and the apical pressure will decrease with the increase of working depth. (2) The large curvature of the root canal can significantly improve the difficulty of irrigation. The curvature of the root canal can severely influence the removal depth of the smear layer on the wall. It can be found both the span and the depth of the ESS for little curvatures (5° and 10°) root canals are higher than those for large curvatures (20° and 30°).
Subject(s)
Dental Pulp Cavity , Smear Layer , Humans , Root Canal Preparation/methods , Hydrodynamics , Root Canal Irrigants/therapeutic use , Root Canal Therapy , Needles , Therapeutic IrrigationABSTRACT
Modification is widely used to enhance the adsorption performance of pristine hydrochar (HBC) and pyrochar (BC). However, comparisons between modified HBC and BC toward pollutant removal have rarely been reported. In this study, pristine HBC and BC derived from rice straw were first produced, and then citric acid (CA) was used as a modifier to synthesize CA-modified HBC (CAHBC) and CA-modified BC (CABC). Furthermore, the adsorption performance of biochars toward methylene blue (MB) was investigated. The results showed that BC exhibits relatively rough surfaces and contains more minerals (ash), whereas HBC has plentiful O-containing functional groups and fewer minerals. CA modification partially removed minerals from the surface of BC, which weakened the ion exchange, surface complexation, and n-π interaction, resulting in a lower adsorption ability toward MB. By contrast, CA produced more O-containing functional groups on the surface of HBC, which strengthened the hydrogen bonding and electrostatic interaction, thus increasing the adsorption capacity toward MB. The two-compartment model showed a good fit to the adsorption process of MB on CAHBC, and the isotherm data for MB adsorption by HBC and CAHBC are suitable for the Freundlich model. The highest adsorption amount of MB using CAHBC was 80.13 mg·g-1, which was 27.66% higher than that for CABC. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analysis indicated that the carboxyl groups in the surface functional groups of CAHBC played a crucial role in the MB adsorption process. In addition, CAHBC showed a good performance for a wide range of pH values (4.0-10.0) and under the interference of coexisting ions, and also presented a recycling ability. Furthermore, the adsorption of MB on CAHBC biochar was a spontaneous, exothermic, degree-of-randomness-increasing process. Consequently, CA modification of HBC is a promising strategy and could be used for MB removal from aquatic environments.