ABSTRACT
Dopamine controls essential brain functions through volume transmission. Different from fast synaptic transmission, where neurotransmitter release and receptor activation are tightly coupled by an active zone, dopamine transmission is widespread and may not necessitate these organized release sites. Here, we determine whether striatal dopamine secretion employs specialized machinery for release. Using super resolution microscopy, we identified co-clustering of the active zone scaffolding proteins bassoon, RIM and ELKS in â¼30% of dopamine varicosities. Conditional RIM knockout disrupted this scaffold and, unexpectedly, abolished dopamine release, while ELKS knockout had no effect. Optogenetic experiments revealed that dopamine release was fast and had a high release probability, indicating the presence of protein scaffolds for coupling Ca2+ influx to vesicle fusion. Hence, dopamine secretion is mediated by sparse, mechanistically specialized active zone-like release sites. This architecture supports spatially and temporally precise coding for dopamine and provides molecular machinery for regulation.
Subject(s)
Axons/metabolism , Corpus Striatum/metabolism , Dopamine/metabolism , Synaptic Transmission/physiology , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Animals , Carrier Proteins/genetics , Carrier Proteins/metabolism , Corpus Striatum/cytology , Dopamine/genetics , Gene Knockdown Techniques , Mice , Mice, Transgenic , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , rab GTP-Binding ProteinsABSTRACT
Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the limiters of energy expenditure are largely unknown. Here, we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to differentiation, obesity, and aging. Assay for transposase-accessible chromatin sequencing (ATAC-seq), ChIP-seq, and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and C/EBPß recruitment to key enhancer regions. These findings expand our understanding of the relationship between inflammatory signaling pathways and adipose tissue function and provide insight into the physiological control of thermogenesis that could inform future therapy.
Subject(s)
Adipocytes/metabolism , Chromatin Assembly and Disassembly , Energy Metabolism , Interleukin-10/metabolism , Thermogenesis , Activating Transcription Factors/metabolism , Animals , CCAAT-Enhancer-Binding Protein-beta/metabolism , Cell Line , Cells, Cultured , Interleukin-10/genetics , Male , Mice , Mice, Inbred C57BL , Signal TransductionABSTRACT
In this issue of Genes & Development, Shapira and colleagues (pp. 660-673) outline mechanisms by which the brown fat transcription factor early B-cell factor 2 (EBF2) selectively activates brown lineage-specific gene expression. The investigators show that EBF2 interacts with and recruits a tissue-specific BAF chromatin remodeling complex to brown fat gene enhancers, thereby regulating chromatin accessibility. Their findings provide important insight into epigenetic regulation of adipocyte fate and thermogenic gene expression.
Subject(s)
Adipose Tissue, Brown , Chromatin , Adipocytes, Brown , B-Lymphocytes , Epigenesis, Genetic , ThermogenesisABSTRACT
Platinum (Pt)-based alloys have received considerable attention due to their compositional variability and unique electrochemical properties. However, homogeneous element distribution at the nanoscale, which is beneficial to various electrocatalytic reactions, is still a great challenge. Herein, a universal approach is proposed to synthesize homogeneously alloyed and size-tunable Pt-based nanoflowers utilizing high gravity technology. Owing to the significant intensification of micro-mixing and mass transfer in unique high gravity shearing surroundings, five typical binary/ternary Pt-based nanoflowers are instantaneously achieved at room temperature. As a proof-of-concept, as-synthesized Platinum-Silver nanoflowers (PtAg NFs) demonstrate excellent catalytic performance and anti-CO poisoning ability for anodic methanol oxidation reaction with high mass activity of 1830 mA mgPt -1, 3.5 and 3.2 times higher than those of conventional beaker products and commercial Pt/C, respectively. The experiment in combination with theory calculations suggest that the enhanced performance is due to additional electronic transmission and optimized d-band center of Pt caused by high alloying degree.
ABSTRACT
Janus-micromotors, as efficient self-propelled materials, have garnered considerable attention for their potential applications in non-agitated liquids. However, the design of micromotors is still challenging and with limited approaches, especially concerning speed and mobility in complex environments. Herein, a two-step spray-drying approach encompassing symmetrical assembly and asymmetrical assembly is introduced to fabricate the metal-organic framework (MOF) Janus-micromotors with hierarchical pores. Using a spray-dryer, a symmetrical assembly is first employed to prepare macro-meso-microporous UiO-66 with intrinsic micropores (<0.5 nm) alongside mesopores (≈24 nm) and macropores (≈400 nm). Subsequent asymmetrical assembly yielded the UiO-66-Janus loaded with the reducible nanoparticles, which underwent oxidation by KMnO4 to form MnO2 micromotors. The micromotors efficiently generated O2 for self-propulsion in H2O2, exhibiting ultrahigh speeds (1135 µm s-1, in a 5% H2O2 solution) and unique anti-gravity diffusion effects. In a specially designed simulated sand-water system, the micromotors traversed from the lower water to the upper water through the sand layer. In particular, the as-prepared micromotors demonstrated optimal efficiency in pollutant removal, with an adsorption kinetic coefficient exceeding five times that of the micromotors only possessing micropores and mesopores. This novel strategy fabricating Janus-micromotors shows great potential for efficient treatment in complex environments.
ABSTRACT
Rheumatoid arthritis (RA), a systemic autoimmune disease, poses a significant human health threat. Iguratimod (IGUR), a novel disease-modifying antirheumatic drug (DMARD), has attracted great attention for RA treatment. Due to IGUR's hydrophobic nature, there's a pressing need for effective pharmaceutical formulations to enhance bioavailability and therapeutic efficacy. The high-gravity nanoprecipitation technique (HGNPT) emerges as a promising approach for formulating poorly water-soluble drugs. In this study, IGUR nanodrugs (NanoIGUR) are synthesized using HGNPT, with a focus on optimizing various operational parameters. The outcomes revealed that HGNPT enabled the continuous production of NanoIGUR with smaller sizes (ranging from 300 to 1000 nm), more uniform shapes, and reduced crystallinity. In vitro drug release tests demonstrated improved dissolution rates with decreasing particle size and crystallinity. Notably, in vitro and in vivo investigations showcased NanoIGUR's efficacy in inhibiting synovial fibroblast proliferation, migration, and invasion, as well as reducing inflammation in collagen-induced arthritis. This study introduces a promising strategy to enhance and broaden the application of poorly water-soluble drugs.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Chromones , Nanoparticles , Sulfonamides , Humans , Polyvinyl Alcohol , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/chemistry , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , WaterABSTRACT
Wound healing has been a persistent clinical challenge for a long time. Electrical stimulation is an effective therapy with the potential to accelerate wound healing. In this work, the self-powered electrospun nanofiber membranes (triples) were constructed as multifunctional wound dressings with electrical stimulation and biochemical capabilities. Triple was composed of a hydrolyzable inner layer with antiseptic and hemostatic chitosan, a hydrophilic core layer loaded with conductive AgNWs, and a hydrophobic outer layer fabricated by self-powered PVDF. Triple exhibited presentable wettability and acceptable moisture permeability. Electrical performance tests indicated that triple can transmit electrical signals formed by the piezoelectric effect to the wound. High antibacterial activities were observed for triple against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with inhibition rates of 96.52, 98.63, and 97.26%, respectively. In vitro cell assays demonstrated that triple cells showed satisfactory proliferation and mobility. A whole blood clotting test showed that triple can enhance hemostasis. The innovative self-powered multifunctional fibers presented in this work offer a promising approach to addressing complications and expediting the promotion of chronic wound healing.
Subject(s)
Anti-Bacterial Agents , Escherichia coli , Nanofibers , Pseudomonas aeruginosa , Staphylococcus aureus , Wound Healing , Wound Healing/drug effects , Nanofibers/chemistry , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Escherichia coli/drug effects , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Chitosan/chemistry , Humans , Animals , Cell Proliferation/drug effectsABSTRACT
An intelligent delivery nanoformulation could enhance the utilization efficacy, uptake, and translocation of pesticides in plants. Herein, a redox/pH-triggered and fluorescent smart delivery nanoformulation was designed and constructed by using hollow mesoporous organosilica nanoparticles (HMONs) and ZnO quantum dots as the nanocarrier and capping agent, respectively. Boscalid was further loaded to generate Boscalid@HMONs@ZnO with a loading rate of 9.8% for controlling Botrytis cinerea (B. cinerea). The quantity of boscalid released by Boscalid@HMONs@ZnO in a glutathione environment or at pH 3.0 was 1.3-fold and 1.9-fold higher than that in a neutral condition. Boscalid@HMONs@ZnO has 1.7-fold the toxicity index of boscalid technical against B. cinerea in antifungal experiments. Pot experiments revealed that the efficacy of Boscalid@HMONs@ZnO was significantly enhanced more than 1.27-fold compared to commercially available water-dispersible granules of boscalid. Due to the fluorescence properties of Boscalid@HMONs@ZnO, pesticide transport's real-time monitoring of pesticide translocation in tomato plants could be observed by confocal laser scanning microscopy. Fluorescence images revealed that HMONs@ZnO had been effectively transported via treated leaves or roots in tomato plants. This research showed the successful application of HMONs@ZnO as a nanocarrier for controlling disease and offered an effective avenue to explore the real-time tracking of pesticide translocation in plants.
Subject(s)
Botrytis , Nanoparticles , Oxidation-Reduction , Zinc Oxide , Botrytis/drug effects , Nanoparticles/chemistry , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Hydrogen-Ion Concentration , Fluorescent Dyes/chemistry , Biphenyl Compounds/chemistry , Quantum Dots/chemistry , Quantum Dots/toxicity , Solanum lycopersicum/chemistry , Pesticides/chemistry , Pesticides/toxicity , Plant Diseases/microbiology , Plant Diseases/prevention & control , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Drug Liberation , Fungicides, Industrial/chemistry , Fungicides, Industrial/pharmacology , Niacinamide/analogs & derivativesABSTRACT
The structure-property relationship of poly(vinyl chloride) (PVC)/CaCO3 nanocomposites is investigated by all-atom molecular dynamics (MD) simulations. MD simulation results indicate that the dispersity of nanofillers, interfacial bonding, and chain mobility are imperative factors to improve the mechanical performance of nanocomposites, especially toughness. The tensile behavior and dissipated work of the PVC/CaCO3 model demonstrate that 12 wt % CaCO3 modified with oleate anion and dodecylbenzenesulfonate can impart high toughness to PVC due to its good dispersion, favorable interface interaction, and weak migration of PVC chains. Under the guidance of MD simulation, we experimentally prepared a transparent PVC/CaCO3 nanocomposite with good mechanical properties by in situ polymerization of monodispersed CaCO3 in vinyl chloride monomers. Interestingly, experimental tests indicate that the optimum toughness of a nanocomposite (a 368% increase in the elongation at break and 204% improvement of the impact strength) can be indeed realized by adding 12 wt % CaCO3 modified with oleic acid and dodecylbenzenesulfonic acid, which is remarkably consistent with the MD simulation prediction. In short, this work provides a proof-of-concept of using MD simulation to guide the experimental synthesis of PVC/CaCO3 nanocomposites, which can be considered as an example to develop other functional nanocomposites.
ABSTRACT
The preservation and accessibility of pores are prerequisites to the application of metal-organic frameworks (MOFs). Activation is a key step to eliciting rich features of pores, but it needs a repeated solvent-exchange process which is tedious and time/cost-consuming. Herein, a facile strategy for highly-efficient activation of MOFs utilizing rotating packed bed is proposed. With the tremendous enhancement of molecular mixing and mass transfer in high-gravity and strong-shearing surrounding, nine representative MOFs are completely activated within 2 h without structural change. Compared with conventional process, this activation displays surprising efficiency by accelerating the diffusion of solvents and redissolution of residual reactants in the pores. The complete activation time can be significantly shortened by over 90%. As a proof-of-concept, the methane storage of as-activated UiO-66 is five times that of as-synthesized UiO-66. This strategy provides a potential platform with industrial worth for the activation of MOF materials with ultra-high efficiency and versatility.
ABSTRACT
Intelligent responsive colloidosomes have attracted increasing attention for their potential to enhance the efficacy and decrease the side effects of drugs in biomedical applications. However, a low encapsulation efficiency and complicated preparation method greatly limit their development. Herein, we report an efficient approach for the construction of pH-stimuli-responsive colloidosomes with high encapsulation efficiency by a high-gravity technology. The conditions under which latex particles with different methacrylic acid contents can successfully self-assemble into colloidosomes are explored. During the preparation process, emulsions emulsified for only 10 min at 2500 rpm in a unique high-gravity shearing surroundings are clarified owing to the greatly enhanced micromixing, while the emulsions emulsified for 30 min by a traditional high-speed shear machine at 4000 rpm are still yellow-white. More importantly, regular spherical colloidosomes encapsulating an anticancer drug doxorubicin not only achieve a small mean diameter of 2.82 µm but also realize a high encapsulation efficiency of 76.5%. The release performance of doxorubicin has an obvious pH-stimuli-responsive regularity and follows the first-order model of sustained release. The construction of intelligent responsive colloidosomes as drug carriers provides a route for controlled drug release and biomedical applications.
ABSTRACT
Controlled pesticide delivery systems offer many distinctive advantages over conventional pesticide formulations. In this work, degradable poly(N-isopropylacrylamide) (PNIPAM)-tannic acid (TA) microgels and multifunctional PDA@PNIPAM-TA nanocomposites were prepared in a high-gravity rotating packed bed reactor (RPB) for smart pesticide delivery and release. The as-prepared microgels and nanocomposites showed reversible temperature-dependent swelling/deswelling behavior and irreversible pH-induced degradation. A dynamic contact angle test suggested that the introduction of TA and PDA into the PNIPAM matrix could enhance foliar adhesion and deposition efficiency. The nanocomposites were further used for the encapsulation and delivery of imidacloprid (IMI) to protect it from rapid photolysis and improve its pest-control efficiency. Their thermoresponsive behavior as well as pesticide loading capacity could be tuned by tailoring the PNIPAM-TA shell thickness, which could be varied by the NIPAM amount. The release rate of IMI from the core/shell nanocomposites was positively correlated with environmental temperature and near-infrared (NIR) light, which was adaptive to the positive temperature-dependent toxicity correlation of IMI and the increasing trend of pests under high temperature. The cumulative release of IMI was 23.5% at 25 °C, while it was 81.2% at 40 °C after 24 h of incubation, and the release rate was greatly enhanced under NIR irradiation. The results indicated that the facile control of pesticide release could be realized by regulating environmental conditions. This work also provides an idea for using high-gravity technology to conveniently construct a smart, effective, and environmentally friendly pesticide delivery system for sustainable crop protection.
ABSTRACT
Extremely inefficient utilization of pesticides has prompted a study of low-cost, sustainable, and smart application systems. Herein, as a promising pesticide nanocarrier, hollow mesoporous organosilica nanoparticles (HMONs) were first synthesized by using inexpensive CaCO3 nanoparticles as the hollow templates. A redox/near-infrared light dual-triggered pesticide release system was further achieved via loading avermectin (AVM) into the HMONs and coating a layer of polydopamine (PDA). The as-prepared AVM@HMONs@PDA displays a favorable pesticide load capability (24.8 wt %), outstanding photothermal performance, and high adhesion to leaves. In addition, with glutathione (GSH), the AVM cumulative release from AVM@HMONs@PDA was 3.5 times higher than that without GSH. Under ultraviolet light irradiation, the half-life of AVM@HMONs@PDA was prolonged by 17.0-fold compared to that of the AVM technical. At day 21 after treatment in the insecticidal activity, the median lethal concentrations (LC50) values displayed that the toxicity of AVM@HMONs@PDA for Panonychus citri (McGregor) was enhanced 4.0-fold compared with the commercial emulsifiable concentrate. In the field trial, at day 28 after spraying, AVM@HMONs@PDA was significantly more control effective than AVM-EC in controlling the P. citri (McGregor), even at a 50% reduced dosage. Moreover, HMONs@PDA was safe for crops. This research presents a novel preparation approach for HMONs, and it also offers a promising nanoplatform for the precise release of pesticides.
Subject(s)
Nanoparticles , Pesticides , Pesticides/toxicity , Nanoparticles/toxicity , Ivermectin/toxicity , Ultraviolet RaysABSTRACT
The design of efficient and sustainable Pt-based catalysts is the key to the development of direct methanol fuel cells. However, most Pt-based catalysts still exhibit disadvantages including unsatisfied catalytic activity and serious CO poisoning in the methanol oxidation reaction (MOR). Herein, highly porous PtAg nanoflowers (NFs) with rich defects are synthesized by using liquid reduction combining chemical etching. It is demonstrated that the proportion of precursors determines the inhomogeneity of alloy elements, and the strong corrosiveness of nitric acid to silver leads to the eventual porous flower-like structure. Impressively, the optimal etched Pt1 Ag2 NFs have the mixed defects of surface steps, dislocations, and bulk holes, and their mass activity (1136 mA mgPt-1 ) is 2.6 times higher than that of commercial Pt/C catalysts, while the ratio of forward and backward peak current density (If /Ib ) can reach 3.2, exhibiting an excellent anti-poisoning ability. Density functional theory calculations further verify their high anti-poison properties from both an adsorption and an oxidation perspective of CO intermediate. The introduction of Ag makes it easier for CO to be oxidized and removed. This study provides a facile approach to prepare rich defects and porous alloy with excellent MOR performance and superior anti-poisoning ability.
Subject(s)
Alloys , Methanol , Alloys/chemistry , Catalysis , Methanol/chemistry , Porosity , SilverABSTRACT
Enhancing the catalytic activity of Pt-based alloy by a rational structural design is the key to addressing the sluggish kinetics of direct alcohol fuel cells. Herein, a facile one-pot method is reported to synthesize PtCuRu nanoflowers (NFs). The synergetic effect among Pt, Cu, and Ru can lower the d-band center of Pt, regulate the morphology, generate Ru-rich edge, and allow the exposure of more high index facets. The optimized Pt0.68 Cu0.18 Ru0.14 NFs exhibit outstanding electrocatalytic performances and excellent anti-poisoning abilities. The specific activities for the methanol oxidation reaction (MOR) (7.65 mA cm-2 ) and ethanol oxidation reaction (EOR) (7.90 mA cm-2 ) are 6.0 and 7.1 times higher than commercial Pt/C, respectively. The CO stripping experiment and the chronoamperometric (5000 s) demonstrate the superior anti-poisoning property and durability performance. Density functional theory calculations confirm that high metallization degree leads to the decrease of d-band center, the promotion of oxidation of CO, and improvement of the inherent activity and anti-poisoning ability. A Ru-rich edge exposes abundant high index facets to accelerate the reaction kinetics of rate-determining steps by decreasing the energy barrier for forming *HCOOH (MOR) and CC bond breaking (EOR).
Subject(s)
Alloys , Ethanol , KineticsABSTRACT
The removal of Cr(VI) has attracted extensive attention since it causes serious harm to public health. Herein, we report a two-step method to synthesize N-doped MoS2 nanoflowers (NFs) with controllable sizes, which are first utilized for Cr(VI) removal and display outstanding removal performance. The N-MoS2 NFs with an average size of 40 nm (N-MoS2 NFs-40 nm) can rapidly remove Cr(VI) in 15 min under optimal conditions. The maximum adsorption capacity of N-MoS2 NFs-40 nm can reach 787.41 mg·g-1, which is significantly larger than that of N-MoS2 NFs-150 and -400 nm (314.46 and 229.88 mg·g-1). Meanwhile, N-MoS2 NFs-400 nm have a higher maximum adsorption capacity than pure MoS2 NFs-400 nm (172.12 mg·g-1). In this adsorption/reduction process, N-MoS2 NFs have abundant adsorption sites due to a high surface area. N doping can generate more sulfur vacancy defects in the MoS2 NF structure to accelerate electron transfer and enhance the reduction of Cr(VI) to low-toxicity Cr(III). This study provides a facile approach to fabricating N-MoS2 nanoflowers and demonstrates their superior removal ability for Cr(VI).
Subject(s)
Molybdenum , Water Pollutants, Chemical , Adsorption , Chromium/analysis , Chromium/chemistry , Water Pollutants, Chemical/analysisABSTRACT
Colloidosomes as Pickering emulsion microcapsules are expected to serve various applications, including encapsulation of drugs and loading of functional materials. Normally, when using colloidosomes for drug encapsulation, the latex particles as shell materials need to be mixed with drugs before the assembly process. However, this procedure may cause aggregation of latex particles, thereby resulting in disordered assembled shells or a low loading efficiency. Herein, we propose a three-fluid nozzle spray drying process to efficiently assemble latex particles of P(styrene (St)-co-butyl acrylate (BA)) into colloidosomes. The three-fluid nozzle spray drying equipment allows for the preparation for drug encapsulation without advance mixing of drug and shell materials. This strategy enables the construction of colloidosomes with uniform and controllable pores and the loading of functional materials. The effects of the compressed air flow rate, inlet temperature, feed rate, and solid content were explored, revealing the formation mechanism of colloidosomes during the spray drying process. Doxycycline hydrochloride (DH) was encapsulated in colloidosomes for controllable release, and the sustained release time is up to 100 h. The release rate can be adjusted by varying the glass transition temperature (Tg) and size of latex particles. Furthermore, Fe3O4 nanoparticle (NP)-loaded colloidosomes were constructed by this strategy. The magnetic response intensity of colloidosomes can be modulated by varying the amount of Fe3O4 NPs. The anticancer drug encapsulation and loading of other functional particles were also explored to expand applications.
Subject(s)
Spray Drying , EmulsionsABSTRACT
BACKGROUND AND AIMS: Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America. METHODS: The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21-day all-cause mortality or requirement for liver transplantation (death/LT). RESULTS: Patients with hypochloremia (<98 mEq/L) had a significantly higher 21-day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant-free cumulative survival in the hypochloremic group than in the normo- or hyper-chloremic groups (log-rank, χ2 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21-day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969-0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13-0.25) but underestimated the probability of transplant-free survival in 34% of patients (NRI = -0.34, 95% CI: -0.39 to -0.28). CONCLUSIONS: Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG-Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT.
Subject(s)
Chlorides , Liver Failure, Acute , Humans , Prognosis , Longitudinal Studies , Liver Failure, Acute/surgery , Proportional Hazards ModelsABSTRACT
Eight versions of the Protocol on Prevention and Control of Coronavirus Disease 2019 (COVID-19) (the Protocol) were issued successively by the Chinese authority to guide the local responses since the first COVID-19 case appeared in Wuhan, China. This study aimed to investigate the evolution of the overall strategy and specific measures in these Protocols, and several recommendations were provided after analysing China's response to the epidemic resurgence. As a result, we found a gradual expanding trend in case surveillance, early screening, and epidemiological investigation, as well as a progressively rigorous tendency in isolation measures and close contact management. With the Protocol's guidance, China had achieved success in several recent fights against domestic COVID-19 resurgences. The city lockdown and multiple city-wide nucleic acid tests adopted were deemed necessary in COVID-19 resurgence's battle. Besides, the large-scale distance centralised quarantine, which is, quarantine in a purpose-built isolation station away from communities where people under quarantine lived, was promoted in rural areas. China's anti-epidemic achievements provide ideas for the global battle against COVID-19.
Subject(s)
COVID-19 , Epidemics , COVID-19/prevention & control , China/epidemiology , Communicable Disease Control , Epidemics/prevention & control , Humans , QuarantineABSTRACT
BACKGROUND: Immunological liver injury (ILI) is a common liver disease and lacks potent drugs for treatment. Artemisia argyi Lévl. et Vant. (A. argyi), a medicinal and edible homologous plant usually used in diet therapy to cure various liver diseases, provides a great option for the prevention of ILI. PURPOSE: To investigate the effect that ethyl acetate extract of A. argyi (AaEA) on Concanavalin A (ConA)-induced ILI and the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. METHODS: The chemical components of AaEA were studied by LC-MS. In animal experiments, the positive control group was administrated diammonium glycyrrhizinate (DIG, 100 mg/kg), while different doses of AaEA groups (AaEA-H, AaEA-M, AaEA-L) were pretreated with AaEA 2.00, 1.00, and 0.50 g/kg, respectively, by intragastric for seven days, once every day. Then, ConA (12.00 mg/kg) was used through tail intravenous injection to establish the ILI model. The blood samples and livers were collected to test the degree of liver dysfunction, inflammation, oxidative stress, histopathological changes, and cell apoptosis. Real-time PCR and Western blotting analysis were used to explain the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. RESULTS: The way in which AaEA prevents liver damage in immunological liver injury (ILI) mice caused by ConA was investigated for the first time. Pretreatment with AaEA reduced the expression of ALT, AST, and inflammatory factors (TNF-α and IFN-γ). Meanwhile, AaEA also reduced MDA levels but upregulated the contents of IL-4, SOD, and GSH-px, alleviating oxidative stress induced by ILI. Western blotting and real-time PCR analysis demonstrated that AaEA could regulate the expression level and relative mRNA expression of key proteins on Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. Finally, 504 components from AaEA were identified by LC-MS analysis, mainly including flavones, phenolic acids, and terpenoids with anti-inflammatory and liver protective activities, which highlights the potential of AaEA for diet treatment of ILI. CONCLUSION: AaEA can work against ConA-induced ILI in mice by regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways, which has the potential to be a great strategy for the prevention of ILI.