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1.
Toxics ; 12(7)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39058169

ABSTRACT

The water quality of sources in the Huaihe River Basin significantly affects the lives and health of approximately 16.7% of China's population. Identifying and quantifying pollution sources and risks is essential for effective water resource management. This study utilized Monte Carlo simulations and Geodetector to assess water quality and eutrophication, as well as to evaluate the sources of heavy metals and the associated health risks for both adults and children. The results showed that eutrophication of water sources in Huaihe River was severe, with an overall EI value of 37.92; 67.8% of the water sources were classified as mesotrophic and 32.2% classified as eutrophic. Water quality and eutrophication levels in the southern mountainous regions were better than those in the densely populated northern areas. Adults were found to have a higher carcinogenic risk than children, whereas children faced a higher noncarcinogenic risk than adults. Cr presented the highest carcinogenic risk, affecting more than 99.8% of both adults and children at levels above 1 × 10-6 but not exceeding 1 × 10-4. The noncarcinogenic risk from metals did not surpass a level of 1, except for Pb. As was primarily influenced by agricultural activities and transportation, whereas Cd, Cr, and Pb were mainly affected by industrial activities, particularly in local textile industries such as knitting and clothing manufacturing. The analysis demonstrated that the influence of anthropogenic factors on heavy metal distribution was significantly enhanced by indirect natural factors. For example, the explanatory power of Precipitation and Road Network Density on As was 0.362 and 0.189, respectively, whereas their interaction had an explanatory power as high as 0.673. This study indicates that the geodetector method is effective in elucidating the factors influencing heavy metal distribution in water, thereby providing valuable insights into pollution sources in global drinking water.

2.
Environ Geochem Health ; 46(8): 280, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963449

ABSTRACT

The chlor-alkali industry (CAI) is crucial for global chemical production; however, its operation has led to widespread heavy metal (HM) contamination at numerous sites, which has not been thoroughly investigated. This study analysed 122 soil and groundwater samples from a typical CAI site in Kaifeng, China. Our aim was to assess the ecological and health risks, identify the sources, and examine the migration characteristics of HMs at this site using Monte Carlo simulation, absolute principal component score-multiple linear regression (APCS-MLR), and the potential environmental risk index (Ei). Our findings revealed that the exceedance rates for Cd, Pb, Hg, and Ni were 71.96%, 45.79%, 49.59%, and 65.42%, respectively. Mercury (Hg) displayed the greatest coefficient of variation across all the soil layers, indicating a significant anthropogenic influence. Cd and Hg were identified as having high and extremely high potential environmental risk levels, respectively. The spatial distributions of the improved Nemerow index (INI), total ecological risk (Ri), and HM content varied considerably, with the most contaminated areas typically associated with the storage of raw and auxiliary materials. Surface aggregation and significant vertical transport were noted for HMs; As and Ni showed substantial accumulation in subsoil layers, severely contaminating the groundwater. Self-organizing maps categorized the samples into two different groups, showing strong positive correlations between Cd, Pb, and Hg. The APCS-MLR model suggested that industrial emissions were the main contributors, accounting for 60.3% of the total HM input. Elevated hazard quotient values for Hg posed significant noncarcinogenic risks, whereas acceptable levels of carcinogenic risk were observed for both adults (96.60%) and children (97.83%). This study significantly enhances historical CAI pollution data and offers valuable insights into ongoing environmental and health challenges.


Subject(s)
Environmental Monitoring , Groundwater , Metals, Heavy , Soil Pollutants , Water Pollutants, Chemical , Metals, Heavy/analysis , China , Groundwater/chemistry , Soil Pollutants/analysis , Risk Assessment , Water Pollutants, Chemical/analysis , Humans , Chemical Industry
3.
J Virol ; 98(7): e0053724, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38934597

ABSTRACT

Various isolates of the Cydia pomonella granulovirus (CpGV) are used as insect pest control agents against codling moth (CM, Cydia pomonella L.), a predominant pest in apple orchards. Three different types (I-III) of dominantly inherited field resistance of CM larvae to CpGV have been recently identified. In this study, transcription of virus genes in midgut cells of type II-resistant CM larvae infected with different CpGV isolates, i.e., CpGV-M and CpGV-S (both prone to type II resistance) as well as CpGV-E2 (breaking type II resistance) was determined by strand-specific RNA sequencing (RNA-Seq) at an early infection stage (72 h post infection). Based on principal component analysis of read counts and the quantitative distribution of single nucleotide polymorphisms (SNPs) in the RNA-Seq data, a bioinformatics analysis pipeline was developed for an a posteriori identification of the infective agents. We report that (i) identification of infective agent is crucial, especially in in vivo infection experiments, when activation of covert virus infections is a possibility, (ii) no substantial difference between CpGV-M and CpGV-S transcription was found in type II-resistant CM larvae despite a different resistance mechanism, (iii) the transcription level of CpGV-M and CpGV-S was much lower than that of CpGV-E2, and (iv) orf59 (sod), orf89 (pif-6), orf92 (p18), and orf137 (lef-10) were identified as significantly downregulated genes in resistance-prone isolates CpGV-M and CpGV-S. For type II resistance of CM larvae, we conclude that CpGV-M and CpGV-S are both able to enter midgut cells, but viral transcription is significantly impaired at an early stage of infection compared to the resistance-breaking isolate CpGV-E2. IMPORTANCE: CpGV is a highly virulent pathogen of codling moth, and it has been developed into one of the most successful commercial baculovirus biocontrol agents for pome fruit production worldwide. The emergence of field resistance in codling moth to commercial CpGV products is a threat toward the sustainable use of CpGV. In recent years, different types of resistance (type I-III) were identified. For type II resistance, very little is known regarding the infection process. By studying the virus gene expression patterns of different CpGV isolates in midguts of type II-resistant codling moth larvae, we found that the type II resistance mechanism is most likely based on intracellular factors rather than a receptor component. By applying SNP mapping of the RNA-Seq data, we further emphasize the importance of identifying the infective agents in in vivo experiments when activation of a covert infection cannot be excluded.


Subject(s)
Gene Expression Profiling , Granulovirus , Larva , Moths , Polymorphism, Single Nucleotide , Animals , Moths/virology , Granulovirus/genetics , Larva/virology , Larva/genetics , RNA-Seq , Pest Control, Biological , Transcriptome , Sequence Analysis, RNA
4.
Medicine (Baltimore) ; 103(19): e38113, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728495

ABSTRACT

To explore the potential mechanism in Cuscuta sinensis on diarrhea-type irritable bowel syndrome using network pharmacology and molecular docking techniques. First, the active components and related targets of Cuscuta were found setting oral utilization >30% and drug-like properties greater than or equal to 0.18 as filter information from TCMSP database. The targets of diarrheal irritable bowel syndrome were compiled by searching DrugBank, GeneCards, OMIM, PharmGkb, and TTD databases. The intersections of drugs and targets related to the disease were taken for gene ontology enrichment and Kyoto encyclopedia of genes and genomes enrichment analyses, to elucidate the potential molecular mechanisms and pathway information of Cuscuta sinensis for the treatment of diarrheal irritable bowel syndrome. The protein-protein interaction network was constructed by using the STRING database and visualized with Cytoscape_v3.10.0 software to find the protein-protein interaction network core At last, molecular docking was performed to validate the combination of active compounds with the core target. The target information of Cuscuta and diarrhea-type irritable bowel syndrome was compiled, which can be resulted in 11 active compounds such as quercetin, kaempferol, isorhamnetin, ß-sitosterol, and another 17 core targets such as TP53, IL6, AKT1, IL1B, TNF, EGFR, etc, whose Kyoto encyclopedia of genes and genomes was enriched in the pathways of lipids and atherosclerosis, chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, and fluid shear stress and atherosclerosis, etc. Docking demonstrated that the core targets and the active compounds were able to be better combined. Cuscuta chinensis may exert preventive effects on diarrhea-type irritable bowel syndrome by reducing intestinal inflammation, protecting intestinal mucosa, and playing an important role in antioxidant response through multi-targets and multi-pathways.


Subject(s)
Cuscuta , Diarrhea , Irritable Bowel Syndrome , Molecular Docking Simulation , Network Pharmacology , Protein Interaction Maps , Irritable Bowel Syndrome/drug therapy , Humans , Diarrhea/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use
5.
Adv Mater ; 36(25): e2311599, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38374796

ABSTRACT

Vertically stacked multiple atomically thin layers have recently widened the landscape of rich optical structures thanks to these quantum metamaterials or van der Waals (vdW) materials, featuring hyperbolic polaritons with unprecedented avenues for light. Despite their far-reaching implications, most of their properties rest entirely on a trivial band topological origin. Here, a 2D approach is adopted toward a micromechanical vdW analogue that, as a result of engineered chiral and mirror symmetries, provides topologically resilient hyperbolic radiation of mechanical vibrations in the ultrasonic regime. By applying laser vibrometry of the micrometer-sized metasurface, we are able to exhibit the exotic fingerprints of robust hyperbolic radiation spanning several frequencies, which beyond their physical relevance, may enable ultrasonic technologies.

6.
Sci Rep ; 14(1): 4932, 2024 02 28.
Article in English | MEDLINE | ID: mdl-38418847

ABSTRACT

One potential approach for treating obesity is to increase energy expenditure in brown and white adipose tissue. Here we aimed to achieve this outcome by targeting mitochondrial uncoupler compounds selectively to adipose tissue, thus avoiding side effects from uncoupling in other tissues. Selective drug accumulation in adipose tissue has been observed with many lipophilic compounds and dyes. Hence, we explored the feasibility of conjugating uncoupler compounds with a lipophilic C8-hydrocarbon chain via an ether bond. We found that substituting the trifluoromethoxy group in the uncoupler FCCP with a C8-hydrocarbon chain resulted in potent uncoupling activity. Nonetheless, the compound did not elicit therapeutic effects in mice, likely as a consequence of metabolic instability resulting from rapid ether bond cleavage. A lipophilic analog of the uncoupler compound 2,6-dinitrophenol, in which a C8-hydrocarbon chain was conjugated via an ether bond in the para-position (2,6-dinitro-4-(octyloxy)phenol), exhibited increased uncoupling activity compared to the parent compound. However, in vivo pharmacokinetics studies suggested that 2,6-dinitro-4-(octyloxy)phenol was also metabolically unstable. In conclusion, conjugation of a hydrophobic hydrocarbon chain to uncoupler compounds resulted in sustained or improved uncoupling activity. However, an ether bond linkage led to metabolic instability, indicating the need to conjugate lipophilic groups via other chemical bonds.


Subject(s)
Adipose Tissue, Brown , Adipose Tissue , Mice , Animals , Adipose Tissue, Brown/metabolism , Adipose Tissue/metabolism , Obesity/metabolism , Energy Metabolism , Adipose Tissue, White/metabolism , Ethers , Phenols/pharmacology , Uncoupling Protein 1/metabolism
7.
Int J Pharm ; 654: 123945, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38403088

ABSTRACT

This study aimed to develop an innovative dosage form for 10-hydroxycamptothecin (HCPT), a chemotherapeutic agent with limited aqueous solubility and stability, to enhance its parenteral delivery and targeting to hepatic cancer. We formulated HCPT into a nanoemulsion using tributyrin, a dietary component with histone deacetylase inhibitor activity. The resulting HCPT-loaded tributyrin nanoemulsion (Tri-HCPT-E) underwent extensive evaluations. Tri-HCPT-E significantly improved the aqueous solubility, stability, and anti-cancer activities in HepG2 cells. Pharmacokinetic studies confirmed the increased stability and hepatic targeting, with Tri-HCPT-E leading to a 120-fold increase in plasma exposure of intact HCPT and a 10-fold increase in hepatic exposure compared to the commercial free solution. Co-administration of 17α-ethynylestradiol, an up-regulator of low-density lipoprotein (LDL) receptor, further enhanced the distribution and metabolism of HCPT, demonstrating an association between the LDL receptor pathway and hepatic targeting. Most importantly, Tri-HCPT-E exhibited superior in vivo anti-cancer efficacy in a mouse xenograft model compared to the commercial formulation, without causing escalated hepatic or renal toxicity. In conclusion, formulating HCPT into a nanoemulsion with tributyrin has proven to be an innovative and effective strategy for targeted hepatic cancer chemotherapy while tributyrin, a pharmacologically active dietary component, has emerged as a promising functional excipient for drug delivery.


Subject(s)
Antineoplastic Agents, Phytogenic , Camptothecin/analogs & derivatives , Liver Neoplasms , Triglycerides , Humans , Mice , Animals , Excipients , Cell Line, Tumor , Liver Neoplasms/drug therapy
8.
Sci Total Environ ; 904: 166857, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37678532

ABSTRACT

Despite the significant reduction in atmospheric pollutant levels during the COVID-19 lockdown, the presence of haze in the North China Plain remained a frequent occurrence owing to the enhanced formation of secondary inorganic aerosols under ammonia-rich conditions. Quantifying the increase or decrease in atmospheric ammonia (NH3) emissions is a key step in exploring the causes of the COVID-19 haze. Historic activity levels of anthropogenic NH3 emissions were collected through various yearbooks and studies, an anthropogenic NH3 emission inventory for Henan Province for 2020 was established, and the variations in NH3 emissions from different sources between COVID-19 and non-COVID-19 years were investigated. The validity of the NH3 emission inventory was further evaluated through comparison with previous studies and uncertainty analysis from Monte Carlo simulations. Results showed that the total NH3 emissions gradually increased from north-west to south-east, totalling 751.80 kt in 2020. Compared to the non-COVID-19 year of 2019, the total NH3 emissions were reduced by approximately 4 %, with traffic sources, waste disposal and biomass burning serving as the sources with the top three largest reductions, approximately 33 %, 9.97 % and 6.19 %, respectively. Emissions from humans and fuel combustion slightly increased. Meanwhile, livestock waste emissions decreased by only 3.72 %, and other agricultural emissions experienced insignificant change. Non-agricultural sources were more severely influenced by the COVID-19 lockdown than agricultural sources; nevertheless, agricultural activities contributed 84.35 % of the total NH3 emissions in 2020. These results show that haze treatment should be focused on reducing NH3, particularly controlling agricultural NH3 emissions.


Subject(s)
Air Pollutants , COVID-19 , Humans , Ammonia/analysis , Air Pollutants/analysis , Pandemics , COVID-19/epidemiology , Communicable Disease Control , Respiratory Aerosols and Droplets , China/epidemiology , Environmental Monitoring
9.
Poult Sci ; 102(6): 102625, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37004288

ABSTRACT

H9N2 is currently the main subtype of avian influenza in China. In order to use reverse genetics to rapid preparation of seed strains for vaccine production, and intend to prevent and control the H9N2 subtype epidemic strains of avian influenza virus (AIV). In this study, we successfully rescued 2 H9N2 recombinant viruses based on the representative viruses of Southeast China and confirmed by RT-PCR and sequencing. Genetic stability, pathogenicity, transmissibility, and antigenicity of 2 recombinant viruses were evaluated. Compared to the FZ1, the growth kinetics of H9N2(HA+NA)/PR8 showed no significant difference, H9N2(HA+NA+M+PB1)/PR8 was slightly lower. Our study also confirmed 2 recombinant viruses had good genetic stability after 10 passages but possessed lower pathogenicity than FZ1. Although both recombinant viruses led to seroconversion in all inoculated birds on 14 dpi, they complete loss of viral transmission of the virus to contact birds. In addition, birds were immunized via hypodermic route by inactivated vaccines of H9N2(HA+NA)/PR8, H9N2(HA+NA+M+PB1)/PR8 and wild-type virus with a single dose, and the results showed that the hemagglutination inhibition titers on 21 dpv were 10.5, 9.6, and 10.5 log2, respectively. And recombinant viruses both provided a certain protection against wild-type virus challenge. In conclusion, these data indicated that 2 recombinant viruses will be expected to be used as inactivated vaccines to controlling the spread of H9N2 subtype AIV even have potential application for attenuated viral vaccines, which provides a reference for the prevention and control of influenza virus pandemics.


Subject(s)
Influenza A Virus, H9N2 Subtype , Influenza Vaccines , Influenza in Birds , Animals , Influenza in Birds/prevention & control , Influenza A Virus, H9N2 Subtype/genetics , Chickens , Virulence , Vaccines, Inactivated
10.
Brain Behav Immun Health ; 28: 100599, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36817510

ABSTRACT

Baicalein (BE) has both antioxidant and anti-inflammatory effects. It has also been reported able to improve cerebral blood circulation in brain ischemic injury. However, its chronic efficacy and metabolomics in Alzheimer's disease (AD) remain unknown. In this study, BE at 80 mg/kg was administrated through the oral route in J20 AD transgenic mice aged from aged 4 months to aged 10 months. Metabolic- and neurobehavioural phenotyping was done before and after 6 months' treatment to evaluate the drug efficacy and the relevant mechanisms. Meanwhile, molecular docking was used to study the binding affinity of BE and poly (ADP-ribose) polymerase-1 (PARP-1) which is related to neuronal injury. The open field test showed that BE could suppress hyperactivity in J20 mice and increase the frequency of the target quadrant crossing in the Morris Water Maze test. More importantly, BE restored cerebral blood flow back to the normal level after the chronic treatment. A 1H NMR-based metabolomics study showed that BE treatment could restore the tricarboxylic acid cycle in plasma. And such a treatment could suppress oxidative stress, inhibit neuroinflammation, alleviate mitochondrial dysfunction, improve neurotransmission, and restore amino homeostasis via starch and sucrose metabolism and glycolipid metabolism in the cortex and hippocampus, which could affect the behavioural and cerebral blood flow. These findings showed that BE is a potential therapeutic agent for AD.

11.
Mol Phylogenet Evol ; 182: 107745, 2023 05.
Article in English | MEDLINE | ID: mdl-36842732

ABSTRACT

Baculoviruses are capable to acquire insect host transposable elements (TEs) in their genomes and are hypothesized as possible vectors of insect transposons between Lepidopteran species. Here, we investigated the host origin of two TEs, namely the Tc1/mariner-like element TCp3.2 and a 0.7 kbp insertion sequence (IS07), found in the genome of different isolates of Cydia pomonella granulovirus (CpGV), a member of the Betabaculovirus genus. The sequences of both TEs were searched for in the full genome sequence database of codling moth (CM, Cydia pomonella L.). A total of eleven TCp3.2 TE copies and 76 copies of the IS07 fragments were identified in the CM genome. These TEs were distributed over the 22 autosomes and the Z chromosome (chr1) of CM, except chr6, chr12, chr16, chr23, chr27 and the W chromosome (chr29). TCp3.2 copies with two transposase genes in opposite direction, representing a novel feature, were identified on chr10 and chr18. The TCp3.2 transposase was characterized by DD41D motif of classic Tc1/mariner transposons, consisting of DNA-binding domain, catalytic domain and nuclear localization signal (NLS). Transcription analyses of uninfected and CpGV-infected CM larvae suggested a doubling of the TCp3.2 transposase transcription rate in virus infected larvae. Furthermore, IS07 insertion into the CpGV genome apparently added new transcription initiation sites to the viral genome. The global analysis of the distribution of two TEs in the genome of CM addressed the influx of mobile TEs from CM to CpGV, a genetic process that contributes to the population diversity of baculoviruses.


Subject(s)
Granulovirus , Moths , Animals , Moths/genetics , Granulovirus/genetics , DNA Transposable Elements , Phylogeny , Transposases/genetics
12.
Sci Total Environ ; 855: 158634, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36089025

ABSTRACT

The diversification or decoupling of production chains from China to alternative Asian countries such as India or Indonesia would impact the spatial distribution of anthropogenic emissions, with corresponding economic impacts due to mortality associated with particulate matter exposure. We evaluated these changes using the Community Earth System Model, the Integrated Exposure-Response (IER) model and Willingness To Pay (WTP) method. Significant effects on PM2.5 related mortality and economic cost for these deaths were seen in many East, Southeast and South Asian countries, particularly those immediately downwind of these three countries. Transferring all of export-related manufacturing to Indonesia resulted in significant mortality decreases in China and South Korea by 78k (5 per 100k) and 1k (2 per 100k) respectively, while Indonesia's mortality significantly increased (73.7k; 29 per 100k), as well as India, Pakistan and Nepal. When production was transferred to India, mortality rates in East Asia show similar changes to the Indonesian scenario, while mortalities in India increased dramatically (87.9k; 6 per 100k), and mortalities in many neighbors of India were also severely increased. Nevertheless, the economic costs for PM2.5 related mortality were much smaller than national GDP changes in China (0.9 % of GDP vs. 18.3 % of GDP), India (2.7 % of GDP vs. 84.3 % of GDP) or Indonesia (9.4 % of GDP vs. 337 % of GDP) due to shifting all of export-related production lines from China to India or Indonesia. Morally, part of the benefits of economic activity should be used to compensate the neighboring communities where mortality increases occur.


Subject(s)
Particulate Matter , Indonesia , China , India , Pakistan
13.
Article in English | MEDLINE | ID: mdl-36231914

ABSTRACT

Air pollution may change people's gym sports behavior. To test this claim, first, we used big data crawler technology and ordinary least square (OLS) models to investigate the effect of air pollution on people' gym visits in Beijing, China, especially under the COVID-19 pandemic of 2019-2020, and the results showed that a one-standard-deviation increase in PM2.5 concentration (fine particulate matter with diameters equal to or smaller than 2.5 µm) derived from the land use regression model (LUR) was positively associated with a 0.119 and a 0.171 standard-deviation increase in gym visits without or with consideration of the COVID-19 variable, respectively. Second, using spatial autocorrelation analysis and a series of spatial econometric models, we provided consistent evidence that the gym industry of Beijing had a strong spatial dependence, and PM2.5 and its spatial spillover effect had a positive impact on the demand for gym sports. Such a phenomenon offers us a new perspective that gym sports can be developed into an essential activity for the public due to this avoidance behavior regarding COVID-19 virus contact and pollution exposure.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Air Pollutants/analysis , Air Pollution/analysis , Beijing/epidemiology , COVID-19/epidemiology , China/epidemiology , Environmental Monitoring/methods , Exercise , Humans , Pandemics , Particulate Matter/analysis
14.
Phys Rev Lett ; 128(10): 104501, 2022 Mar 11.
Article in English | MEDLINE | ID: mdl-35333072

ABSTRACT

In this Letter, we introduce a new paradigm for achieving robust asymmetric generation of acoustic vortex field through dual-layer metasurfaces by controlling their intrinsic topologic charges and the parity of geometry design. The underlying physics is contributed to the one-way process of orbital angular momentum (OAM) transition ensured by the broken spatial symmetry and the external topologic charge from the vortex diffraction. We further experimentally demonstrate this novel phenomenon. Our findings could provide new routes to manipulate the asymmetric response of vortex fields, including one-way excitation and propagation, and promise potential applications in passive OAM-based diodes.

15.
Int J Pharm ; 591: 119981, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33069896

ABSTRACT

The application of baicalein (BE) in central nervous system (CNS) neurodegenerative diseases is hampered by its poor solubility and low oral bioavailability despite its neuroprotective effects. In this study, BE was encapsulated into poly (ethylene glycol)-block-poly (D, L-lactide) micelles (BE-MC) and administrated through nasal inhalation to enhance its brain distribution. BE-MC showed comparable in-vitro antioxidant activity to BE solution. Cytotoxicity study illustrated BE-MC could reduce BE's toxicity in SH-SY5Y cells and BV-2 cells. BE solution at concentration higher than 5 µM caused significant BV-2 cells' death after stimulation of LPS while BE-MC were non-toxic to cells at concentrations up to 50 µM. BE solution at 5 µM had no anti-inflammatory effects in BV-2 cells while BE-MC could reduce the inflammatory factor TNF-α at 5 µM and IL-6 at 20 µM significantly. Pharmacokinetic studies in C57BL/6 mice showed the absolute AUC values of BE in plasma and brain of BE-MC through nasal inhalation group were 5.09-fold and 1.50-fold higher than that of BE coarse powder through oral administration group at the same dose. Thus, our study indicated BE-MC administered nasally could be useful for treatment of CNS neurodegenerative diseases due to oxidative stress and inflammation.


Subject(s)
Micelles , Neurodegenerative Diseases , Animals , Brain , Dioxanes , Drug Carriers , Flavanones , Inflammation/drug therapy , Mice , Mice, Inbred C57BL , Neurodegenerative Diseases/drug therapy , Oxidative Stress , Polyesters , Polyethylene Glycols
16.
Mol Pharm ; 17(11): 4256-4269, 2020 11 02.
Article in English | MEDLINE | ID: mdl-33084343

ABSTRACT

Curcumin (CUR) has antioxidant and anti-inflammatory effects that are beneficial to Alzheimer's disease (AD). However, the poor solubility and high instability of CUR compromise its application greatly. In this study, CUR-encapsulated chitosan-coated poly (lactic-co-glycolic acid) nanoparticles (CUR-CS-PLGA-NPs) and hydroxypropyl-ß-cyclodextrin-encapsulated CUR complexes (CUR/HP-ß-CD inclusion complexes) were developed and compared through intranasal administration. In vitro studies indicated that CUR in CUR/HP-ß-CD inclusion complexes was stable under physiological conditions over 72 h with 95.41 ± 0.01% remaining, which was higher than 49.66 ± 3.91% remaining in CUR-CS-PLGA-NPs. Meanwhile, CUR/HP-ß-CD inclusion complexes showed a higher cellular uptake level of CUR than CUR-CS-PLGA-NPs in SH-SY5Y cells. Both formulations could reduce CUR's cellular cytotoxicity and showed a comparable antioxidant effect. Both formulations displayed the anti-inflammatory effect at 20 µM CUR in BV-2 cells, which decreased TNF-α and IL-6 levels to approximately 70 and 40%, respectively, when compared to the positive control, respectively. In vivo pharmacokinetic studies indicated that after intranasal administration, the AUC values of CUR in the plasma and brain of the CUR/HP-ß-CD inclusion complex group were 2.57-fold and 1.12-fold higher than those in the CUR-CS-PLGA-NP group at the same dose of 2 mg/kg, respectively. In conclusion, CUR/HP-ß-CD inclusion complexes displayed better properties than CUR-CS-PLGA-NPs as a carrier for intranasal delivery of CUR for application in AD.


Subject(s)
2-Hydroxypropyl-beta-cyclodextrin/chemistry , Alzheimer Disease/drug therapy , Anti-Inflammatory Agents/administration & dosage , Antioxidants/administration & dosage , Chitosan/chemistry , Curcumin/administration & dosage , Drug Carriers/chemistry , Nanoparticles/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Administration, Intranasal , Animals , Anti-Inflammatory Agents/pharmacokinetics , Antioxidants/pharmacokinetics , Cell Line, Tumor , Curcumin/pharmacokinetics , Drug Compounding/methods , Drug Stability , Humans , Male , Mice , Mice, Inbred C57BL , Solubility
17.
Pest Manag Sci ; 76(4): 1363-1370, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31605411

ABSTRACT

BACKGROUND: Baculoviruses provide long-lasting control of crop pests and are harmless to humans and non-target animals, making them attractive bioinsecticides. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has a wide-host range and is one such commercial bioinsecticide, but its low infectivity to older larvae and less-sensitive species precludes its large-scale application. We sought to improve the infectivity of AcMNPV. RESULTS: Two enhancing factors, the truncated enhancin from Agrotis segetum granulovirus and GP37 from Cydia pomonella granulovirus, were expressed in fusion with the N-terminal and middle domain of the polyhedrin envelope protein of AcMNPV. Western blotting and immunoelectron microscopy analysis indicated that the enhancing factors were expressed on the occlusion bodies of the resulting AcMNPV variants. Bioassays showed that the median lethal doses of the recombinant viruses were 3.9-fold to 7.4-fold lower than those of the wild-type virus against the second and fourth instar of Spodoptera exigua larvae. The yields of occlusion bodies from the two recombinants in S. exigua larvae were comparable with those of the wild-type virus both in vitro and in vivo. Further bioassays showed that the AcMNPV variants fusing the enhancing factors were incapable of infecting the second instar larvae of S. litura, Helicoverpa armigera, and Pyrausta nubilalis, which were not sensitive to the wild-type AcMNPV. CONCLUSION: These genetically modified AcMNPV variants exhibited an enhanced infectivity and may offer better baculovirus control of crop pests. © 2019 Society of Chemical Industry.


Subject(s)
Baculoviridae , Moths , Animals , Larva , Spodoptera
18.
Virol Sin ; 35(1): 43-51, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31552609

ABSTRACT

Beak and feather disease virus (BFDV) is an infectious agent responsible for feather degeneration and beak deformation in birds. In March 2017, an epidemic of psittacine beak and feather disease (PBFD) struck a farm in Fuzhou in the Fujian Province of southeast China, resulting in the death of 51 parrots. In this study, the disease was diagnosed and the pathogen was identified by PCR and whole genome sequencing. A distinct BFDV strain was identified and named as the FZ strain. This BFDV strain caused severe disease symptoms and pathological changes characteristic of typical PBFD in parrots, for example, loss of feathers and deformities of the beak and claws, and severe pathological changes in multiple organs of the infected birds. Phylogenetic analysis showed that the FZ strain was more closely related to the strain circulating in New Caledonia than the strains previously reported in China. Nucleotide homology between the FZ strain and other 43 strains of BFDV ranged from 80.0% to 92.0%. Blind passage experiment showed that this strain had limited replication capability in SPF Chicken Embryos and DF-1 Cells. Furthermore, the capsid (Cap) gene of this FZ strain was cloned into the pGEX-4T-1 expression vector to prepare the polyclonal anti-Cap antibody. Western blotting analysis using the anti-Cap antibody further confirmed that the diseased parrots were infected with BFDV. In this study, a PBFD and its pathogen was identified for the first time in Fujian Province of China, suggesting that future surveillance of BFDV should be performed.


Subject(s)
Bird Diseases/virology , Circoviridae Infections/veterinary , Circovirus/classification , Parrots/virology , Phylogeny , Animals , Beak/pathology , Beak/virology , Bird Diseases/epidemiology , Capsid Proteins/genetics , China , Circoviridae Infections/virology , Circovirus/isolation & purification , Farms , Feathers/pathology , Feathers/virology , Feces/virology , Genome, Viral , Whole Genome Sequencing
19.
Mol Neurobiol ; 56(11): 7267-7283, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31016475

ABSTRACT

Identification of molecular mechanisms underlying early-stage Alzheimer's disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics approach was employed to investigate the metabolic profiles in plasma and brain tissues harvested from 5-month-old APP/PS1 transgenic mice and their wildtype counterparts. Since different brain regions were expected to have their own distinct metabolic signals, four different brain regions, namely cortex, hippocampus, midbrain and cerebellum tissues, were dissected and had their metabolic profiles studied separately. Biochemical assays were also performed on plasma and brain cortex tissue of transgenic mice and wildtype mice, with a focus on mitochondrial health. Amyloid precursor protein and amyloid-ß levels in plasma, brain cortex tissue and mitochondria fractions isolated from brain cortex were measured to assess the amyloid pathology. Our findings include the observation of extensive metabolic alterations in cortex and cerebellum of APP/PS1 mice, but not in their hippocampus, midbrain and plasma. The major pathways affected in cortex and cerebellum of APP/PS1 mice were closely related to impaired energy metabolism and perturbation of amino acid metabolism in these mice. APP/PS1 mice also exhibited higher amyloid-ß40 and amyloid-ß42 in their cortex, accumulation of mitochondria APP in their cortex, and presented an altered oxidative state in their brain. Treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone (PIO) successfully restored the energy metabolism, lowered amyloid-ß levels and afforded the APP/PS1 mice a better antioxidative capacity in their cortex.


Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/metabolism , Cerebellum/metabolism , Cerebral Cortex/metabolism , PPAR gamma/agonists , Pioglitazone/therapeutic use , Presenilin-1/metabolism , Alzheimer Disease/blood , Amyloid beta-Protein Precursor/blood , Animals , Catalase/metabolism , Citrate (si)-Synthase/metabolism , Discriminant Analysis , Disease Models, Animal , Female , Hippocampus/metabolism , L-Lactate Dehydrogenase/metabolism , Male , Metabolomics , Mice, Transgenic , Mitochondria/drug effects , Mitochondria/metabolism , Pioglitazone/pharmacology , Principal Component Analysis , Superoxide Dismutase/metabolism
20.
RSC Adv ; 9(18): 9946-9950, 2019 Mar 28.
Article in English | MEDLINE | ID: mdl-35520928

ABSTRACT

Tin oxide (SnO2) is widely used as electron transport layer (ETL) material in perovskite solar cells (PSCs). Numerous synthesis methods for SnO2 have been reported, but they all require a proper thermal treatment for the SnO2 ETLs. Herein we present a simple method to synthesize SnO2 nanoparticles (NPs) at room temperature. By using butyl acetate as a precipitator and a proper UV-Ozone treatment to remove Cl residuals, excellent SnO2 ETLs were obtained without any thermal annealing. The highest power conversion efficiency (PCE) of the prepared PSCs was 19.22% for reverse scan (RS) and 18.79% for forward scan (FS). Furthermore, flexible PSCs were fabricated with high PCEs of 15.27%/14.74% (RS/FS). The low energy consuming SnO2 ETLs therefore show great promise for the flexible PSCs' commercialization.

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