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1.
PLoS Genet ; 18(10): e1010455, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36206313

RESUMO

Many plant secondary substances are feeding deterrents for insects and play a key role in the selection of host plants. The taste sensilla of phytophagous insects contain gustatory sensory neurons sensitive to deterrents but the molecular basis of deterrent chemoreception remains unknown. We investigated the function of Gr180, the most highly expressed bitter gustatory receptor in the maxillary galea of Helicoverpa armigera larvae. Functional analyses using the Xenopus oocyte expression system and two-electrode voltage clamp revealed that the oocytes expressing Gr180 responded to coumarin. Tip recording results showed that the medial sensilla styloconica of the maxilla of fifth instar larvae exhibited electrophysiological responses to coumarin. Two-choice feeding bioassays confirmed that coumarin inhibited larval feeding. A homozygous mutant strain of H. armigera with truncated Gr180 proteins (Gr180-/-) was established using the CRISPR-Cas9 system. The responses of the medial sensilla styloconica in Gr180-/- to coumarin were almost abolished, and the responses to sinigrin and strychnine were also significantly decreased. Knockout of Gr180 alleviated the feeding deterrent effects of coumarin, sinigrin, and strychnine. Thus, we conclude that Gr180 is a receptor responding to coumarin,and also participates in sensing sinigrin and strychnine. These results enhance our understanding of the gustatory sensing mechanisms of phytophagous insects to deterrents.


Assuntos
Mariposas , Paladar , Animais , Larva/metabolismo , Paladar/genética , Estricnina/metabolismo , Estricnina/farmacologia , Maxila/metabolismo , Mariposas/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Cumarínicos/metabolismo , Cumarínicos/farmacologia
2.
Proc Natl Acad Sci U S A ; 119(49): e2215442119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36442117

RESUMO

Sex pheromones are pivotal for insect reproduction. However, the mechanism of sex pheromone communication remains enigmatic in hymenopteran parasitoids. Here we have identified the sex pheromone and elucidated the olfactory basis of sex pheromone communication in Campoletis chlorideae (Ichneumonidae), a solitary larval endoparasitoid of over 30 lepidopteran pests. Using coupled gas chromatography-electroantennogram detection, we identified two female-derived pheromone components, tetradecanal (14:Ald) and 2-heptadecanone (2-Hep) (1:4.6), eliciting strong antennal responses from males but weak responses from females. We observed that males but not females were attracted to both single components and the blend. The hexane-washed female cadavers failed to arouse males, and replenishing 14:Ald and 2-Hep could partially restore the sexual attraction of males. We further expressed six C. chlorideae male-biased odorant receptors in Drosophila T1 neurons and found that CchlOR18 and CchlOR47 were selectively tuned to 14:Ald and 2-Hep, respectively. To verify the biological significance of this data, we knocked down CchlOR18 and CchlOR47 individually or together in vivo and show that the attraction of C. chlorideae to their respective ligands was abolished. Moreover, the parasitoids defective in either of the receptors were less likely to court and copulate. Finally, we show that the sex pheromone and (Z)-jasmone, a potent female attractant, can synergistically affect behaviors of virgin males and virgin females and ultimately increase the parasitic efficiency of C. chlorideae. Our study provides new insights into the molecular mechanism of sex pheromone communication in C. chlorideae that may permit manipulation of parasitoid behavior for pest control.


Assuntos
Receptores Odorantes , Atrativos Sexuais , Masculino , Animais , Insetos , Comunicação , Feromônios , Drosophila
3.
Nano Lett ; 24(29): 9104-9114, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39007505

RESUMO

Tumor-associated macrophages (TAMs), as the most prevalent immune cells in the tumor microenvironment, play a pivotal role in promoting tumor development through various signaling pathways. Herein, we have engineered a Se@ZIF-8 core-satellite nanoassembly to reprogram TAMs, thereby enhancing immunotherapy outcomes. When the nanoassembly reaches the tumor tissue, selenium nanoparticles and Zn2+ are released in response to the acidic tumor microenvironment, resulting in a collaborative effort to promote the production of reactive oxygen species (ROS). The generated ROS, in turn, activate the nuclear factor κB (NF-κB) signaling pathway, driving the repolarization of TAMs from M2-type to M1-type, effectively eliminating cancer cells. Moreover, the nanoassembly can induce the immunogenic death of cancer cells through excess ROS to expose calreticulin and boost macrophage phagocytosis. The Se@ZIF-8 core-satellite nanoassembly provides a potential paradigm for cancer immunotherapy by reversing the immunosuppressive microenvironment.


Assuntos
Imunoterapia , Espécies Reativas de Oxigênio , Selênio , Microambiente Tumoral , Macrófagos Associados a Tumor , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Animais , Humanos , Selênio/química , Selênio/farmacologia , Neoplasias/terapia , Neoplasias/imunologia , NF-kappa B/metabolismo , Nanopartículas/química , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Reprogramação Celular/efeitos dos fármacos , Fagocitose/efeitos dos fármacos
4.
PLoS Genet ; 17(7): e1009527, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34264948

RESUMO

Glucosinolates are token stimuli in host selection of many crucifer specialist insects, but the underlying molecular basis for host selection in these insects remains enigmatic. Using a combination of behavioral, electrophysiological, and molecular methods, we investigate glucosinolate receptors in the cabbage butterfly Pieris rapae. Sinigrin, as a potent feeding stimulant, elicited activity in larval maxillary lateral sensilla styloconica, as well as in adult medial tarsal sensilla. Two P. rapae gustatory receptor genes PrapGr28 and PrapGr15 were identified with high expression in female tarsi, and the subsequent functional analyses showed that Xenopus oocytes only expressing PrapGr28 had specific responses to sinigrin; when ectopically expressed in Drosophila sugar sensing neurons, PrapGr28 conferred sinigrin sensitivity to these neurons. RNA interference experiments further showed that knockdown of PrapGr28 reduced the sensitivity of adult medial tarsal sensilla to sinigrin. Taken together, we conclude that PrapGr28 is a gustatory receptor tuned to sinigrin in P. rapae, which paves the way for revealing the molecular basis of the relationships between crucifer plants and their specialist insects.


Assuntos
Borboletas/fisiologia , Glucosinolatos , Proteínas de Insetos/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Brassica , Borboletas/efeitos dos fármacos , Drosophila/genética , Feminino , Regulação da Expressão Gênica , Glucosinolatos/farmacologia , Proteínas de Insetos/genética , Larva , Oócitos/metabolismo , Receptores de Superfície Celular/genética , Percepção Gustatória , Xenopus
5.
Nano Lett ; 23(8): 3369-3376, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37052625

RESUMO

Lithium (Li) metal has attracted great attention as a promising high-capacity anode material for next-generation high-energy-density rechargeable batteries. Nonuniform Li+ transport and uneven Li plating/stripping behavior are two key factors that deteriorate the electrochemical performance. In this work, we propose an interphase acid-base interaction effect that could regulate Li plating/stripping behavior and stabilize the Li metal anode. ZSM-5, a class of zeolites with ordered nanochannels and abundant acid sites, was employed as a functional interface layer to facilitate Li+ transport and mitigate the cell concentration polarization. As a demonstration, a pouch cell with a high-areal-capacity LiNi0.95Co0.02Mn0.03O2 cathode (3.7 mAh cm-2) and a ZSM-5 modified thin lithium anode (50 µm) delivered impressive electrochemical performance, showing 92% capacity retention in 100 cycles (375.7 mAh). This work reveals the effect of acid-base interaction on regulating lithium plating/stripping behaviors, which could be extended to developing other high-performance alkali metal anodes.

6.
Gynecol Oncol ; 171: 39-48, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36804620

RESUMO

OBJECTIVE: Sirtuin-7 (SIRT7) is a class III histone deacetylase that plays an important role in cancer development and frequently overexpressed in carcinomas. In this study, the tumor-supporting role and underlying mechanisms of SIRT7 were characterized in ovarian cancer (OC) aggressiveness. METHODS: SIRT7 expression was examined in OC tissues and cells. Interactions among SIRT7, GATA4, Wnt signaling pathway were explored by bioinformatics tools and experimental validations. The effect of SIRT7 and GATA4 on malignant phenotypes of OC cells were examined with gain- and loss-of-function experiments. A nude mouse model of OC was developed to verify the in vitro findings. RESULTS: It was noted that SIRT7 was highly expressed in OC tissues and cells. Cell lines with higher SIRT7 expression (OVCAR-3 and OVCAR-8) were used for subsequent in vitro experiments. The experimental data indicated that silencing of SIRT7 suppressed the OC cell proliferation, colony formation, migration, and invasion, and promoted cell senescence, which could be abolished by GATA4 knockdown. Mechanistically, SIRT7 promoted deacetylation of GATA4 and consequently inhibited the transcriptional activity of GATA4. In addition, GATA4 induced OC cell senescence by inhibiting Wnt signaling pathway. Further in vivo experiments substantiated that SIRT7 knockdown or overexpressed GATA4 could effectively inhibit tumor growth of nude mice. CONCLUSION: Taken together, our findings indicated that SIRT7 enhanced development of OC by suppressing GATA4 and activating Wnt signaling pathway, suggesting the potential of SIRT7/GATA4/Wnt axis as a therapeutic target for OC.


Assuntos
Neoplasias Ovarianas , Sirtuínas , Animais , Camundongos , Humanos , Feminino , Via de Sinalização Wnt , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Apoptose/genética , Camundongos Nus , Sirtuínas/genética , Sirtuínas/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo
7.
BMC Biol ; 20(1): 214, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36175945

RESUMO

BACKGROUND: Odorant receptors (ORs) as odorant-gated ion channels play a crucial role in insect olfaction. They are formed by a heteromultimeric complex of the odorant receptor co-receptor (Orco) and a ligand-selective Or. Other types of olfactory receptor proteins, such as ionotropic receptors (IRs) and some gustatory receptors (GRs), are also involved in the olfactory system of insects. Orco as an obligatory subunit of ORs is highly conserved, providing an opportunity to systematically evaluate OR-dependent olfactory responses. RESULTS: Herein, we successfully established a homozygous mutant (Orco-/-) of Helicoverpa armigera, a notorious crop pest, using the CRISPR/Cas9 gene editing technique. We then compared the olfactory response characteristics of wild type (WT) and Orco-/- adults and larvae. Orco-/- males were infertile, while Orco-/- females were fertile. The lifespan of Orco-/- females was longer than that of WT females. The expressions of most Ors, Irs, and other olfaction-related genes in adult antennae of Orco-/- moths were not obviously affected, but some of them were up- or down-regulated. In addition, there was no change in the neuroanatomical phenotype of Orco-/- moths at the level of the antennal lobe (including the macroglomerular complex region of the male). Using EAG and SSR techniques, we discovered that electrophysiological responses of Orco-/- moths to sex pheromone components and many host plant odorants were absent. The upwind flight behaviors toward sex pheromones of Orco-/- males were severely reduced in a wind tunnel experiment. The oviposition selectivity of Orco-/- females to the host plant (green pepper) has completely disappeared, and the chemotaxis toward green pepper was also lost in Orco-/- larvae. CONCLUSIONS: Our study indicates that OR-mediated olfaction is essential for pheromone communication, oviposition selection, and larval chemotaxis of H. armigera, suggesting a strategy in which mate searching and host-seeking behaviors of moth pests could be disrupted by inhibiting or silencing Orco expression.


Assuntos
Mariposas , Receptores Odorantes , Atrativos Sexuais , Animais , Feminino , Masculino , Eletrólitos , Proteínas de Insetos/metabolismo , Canais Iônicos , Larva/genética , Larva/metabolismo , Ligantes , Mariposas/genética , Mutagênese , Feromônios , Receptores Odorantes/metabolismo , Olfato
8.
Epidemiol Infect ; 150: e117, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35610736

RESUMO

In the past 10-15 years, the government of China has made various efforts in tackling excessive antibiotics use. Yet, little is known about their effects at rural primary care settings. This study aimed to determine the impact of government policies and the COVID-19 pandemic on antibiotic prescribing practices at such settings utilizing data from separate studies carried out pre- and during the pandemic, in 2016 and 2021 in Anhui province, China, using identical sampling and survey approaches. Data on antibiotics prescribed, diagnosis, socio-demographic, etc., were obtained through non-participative observation and a structured exit survey. Data analysis comprised mainly descriptive comparisons of 1153 and 762 patients with respiratory infections recruited in 2016 and 2021, respectively. The overall antibiotics prescription rate decreased from 89.6% in 2016 to 69.1% in 2021, and the proportion of prescriptions for two or more classes of antibiotics was estimated as 35.9% in 2016 and 11.0% in 2021. There was a statistically significant decrease in the number of days from symptom onset to clinic visits between the year groups. In conclusion, measures to constrain excessive prescription of antibiotics have led to some improvements at the rural primary care level, and the COVID-19 pandemic has had varying effects on antibiotic use.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Infecções Respiratórias , Antibacterianos/uso terapêutico , COVID-19/epidemiologia , China/epidemiologia , Humanos , Pandemias , Padrões de Prática Médica , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia
9.
J Med Internet Res ; 24(10): e37648, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36114000

RESUMO

BACKGROUND: Home blood pressure telemonitoring (HBPT) is witnessing rapid diffusion worldwide. Contemporary studies documented mainly short-term (6-12 months) effects of HBPT, and there are limited data about its uptake. OBJECTIVE: The aim of this study was to explore the 3-year use and determinants of HBPT, and the interactions with systolic and diastolic blood pressure (SBP/DBP) and overall blood pressure (BP) control rate. METHODS: HBPT records were obtained from a 3-year cohort of 5658 patients with hypertension in Jieshou, Anhui, China, and data from a structured household survey of a random sample (n=3005) of the cohort. The data analysis comprised (1) timeline trajectories of the rates of monthly active HBPT and mean SBP/DBP for overall and subgroups of patients with varied start-month SBP/DBP; and (2) multivariable linear, logistic, and percentile regression analyses using SBP/DBP, BP control rate, and yearly times of HBPT as the dependent variable, respectively. RESULTS: HBPT was followed by mixed changes in mean monthly SBP/DBP for varied patient groups. The magnitude of changes ranged from -43 to +39 mmHg for SBP and from -27 to +15 mmHg for DBP. The monthly rates of active HBPT all exhibited a rapid and then gradually slower decline. When controlled for commonly reported confounders, times of HBPT in the last year were found to have decreasing correlation coefficients for SBP/DBP (from 0.16 to -0.35 and from 0.11 to -0.35, respectively) and for BP control rate (from 0.53 to -0.62). CONCLUSIONS: HBPT had major and "target-converging" effects on SBP/DBP. The magnitude of changes was much greater than commonly reported. BP, variation in BP, and time were the most important determinants of HBPT uptake. Age, education, duration of hypertension, family history, and diagnosis of hypertension complications were also linked to the uptake but at weaker strength. There is a clear need for differentiated thinking over the application and assessment of HBPT, and for identifying and correcting/leveraging potential outdated/new opportunities or beliefs.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertensão , Pressão Sanguínea , Determinação da Pressão Arterial , Estudos de Coortes , Humanos , Hipertensão/diagnóstico
10.
Nano Lett ; 21(7): 3127-3133, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33734706

RESUMO

Silicon (Si)-based material is a promising anode material for next-generation lithium-ion batteries (LIBs). Herein, we report the fabrication of a silicon oxide-carbon (SiOx/C) nanocomposite through the reaction between silicon particles with fresh surface and H2O in a mild hydrothermal condition, as well as conducting carbon coating synchronously. We found that controllable oxidation could be realized for Si particles to produce uniform SiOx after the removal of the native passivation layer. The uniform oxidation and conductive coating offered the as-fabricated SiOx/C composite good stability at both particle and electrode level over electrochemical cycling. The as-fabricated SiOx/C composite delivered a high reversible capacity of 1133 mAh g-1 at 0.5 A g-1 with 89.1% capacity retention after 200 cycles. With 15 wt % SiOx/C composite, graphite-SiOx/C hybrid electrode displayed a high reversible specific capacity of 496 mAh g-1 and stable electrochemical cycling with a capacity retention of 90.1% for 100 cycles.

11.
Nano Lett ; 21(15): 6656-6663, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34291943

RESUMO

Lithium-sulfur (Li-S) batteries suffer from sluggish sulfur redox reactions under high-sulfur-loading and lean-electrolyte conditions. Herein, a typical Co@NC heterostructure composed of Co nanoparticles and a semiconductive N-doped carbon matrix is designed as a model Mott-Schottky catalyst to exert the electrocatalytic effect on sulfur electrochemistry. Theoretical and experimental results reveal the redistribution of charge and a built-in electric field at the Co@NC heterointerface, which are critical to lowering the energy barrier of polysulfide reduction and Li2S oxidation in the discharge and charge process, respectively. With Co@NC Mott-Schottky catalysts, the Li-S batteries display an ultrahigh capacity retention of 92.1% and a system-level gravimetric energy density of 307.8 Wh kg-1 under high S loading (10.73 mg cm-2) and lean electrolyte (E/S = 5.9 µL mgsulfur-1) conditions. The proposed Mott-Schottky heterostructure not only deepens the understanding of the electrocatalytic effect in Li-S chemistry but also inspires a rational catalyst design for advanced high-energy-density batteries.

12.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077444

RESUMO

The closely related species Helicoverpa armigera (H. armigera) and Helicoverpa assulta (H. assulta) have different host plant ranges and share two principal components of sex pheromones but with reversed ratios. The antennae are the main olfactory organ of insects and play a crucial role in host plant selection and mate seeking. However, the genetic basis for gene expression divergence in the antennae of the two species is unclear. We performed an allele-specific expression (ASE) analysis in the antennal transcriptomes of the two species and their F1 hybrids, examining the connection between gene expression divergence and phenotypic differences. The results show that the proportion of genes classified as all cis was higher than that of all trans in males and reversed in females. The contribution of regulatory patterns to gene expression divergence in males was less than that in females, which explained the functional differentiation of male and female antennae. Among the five groups of F1 hybrids, the fertile males from the cross of H. armigera female and H. assulta male had the lowest proportion of misexpressed genes, and the inferred regulatory patterns were more accurate. By using this group of F1 hybrids, we discovered that cis-related regulations play a crucial role in gene expression divergence of sex pheromone perception-related proteins. These results are helpful for understanding how specific changes in the gene expression of olfactory-related genes can contribute to rapid evolutionary changes in important olfactory traits in closely related moths.


Assuntos
Mariposas , Atrativos Sexuais , Animais , Antenas de Artrópodes/metabolismo , Feminino , Masculino , Mariposas/genética , Mariposas/metabolismo , Atrativos Sexuais/genética , Atrativos Sexuais/metabolismo , Olfato/genética , Transcriptoma
13.
J Am Chem Soc ; 143(8): 3143-3152, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33595314

RESUMO

Metal anodes represent as a prime choice for the coming generation rechargeable batteries with high energy density. However, daunting challenges including electrode volume variation and inevitable side reactions preclude them from becoming a viable technology. Here, a facile replacement reaction was employed to fabricate a three-dimensional (3D) interdigitated metal/solid electrolyte composite electrode, which not only provides a stable host structure for buffering the volume change within the composite but also prevents side reactions by avoiding the direct contact between active metal and liquid electrolyte. As a proof-of-concept demonstration, a 3D interdigitated zinc (Zn) metal/solid electrolyte architecture was fabricated via a galvanic replacement reaction between Zn metal foil and indium (In) chloride solution followed by electrochemical activation, featuring the interdigitation between metallic Zn and amorphous indium hydroxide sulfate (IHS) with high Zn2+ conductivity (56.9 ± 1.8 mS cm-1), large Zn2+ transference number (0.55), and high electronic resistivity [(2.08 ± 0.01) × 103 Ω cm]. The as-designed Zn/IHS electrode sustained stable electrochemical Zn plating/stripping over 700 cycles with a record-low overpotential of 8 mV at 1 mA cm-2 and 0.5 mAh cm-2. More impressively, it displayed cycle-stable performance with low overpotential of 10 mV under ultrahigh current density and areal capacity (20 mA cm-2, 20 mAh cm-2), which outperformed all the reported Zn metal electrodes in mild aqueous electrolyte. The fabrication of interdigitated metal/solid electrolyte was generalized to other metal pairs, including Zn/Sn and Zn/Co, which provide inspiration for next-generation Zn metal batteries with high energy density and reversibility.

14.
J Gene Med ; 22(11): e3247, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32602607

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) is a carcinogenic lncRNA in diverse cancers. The expression pattern and mechanisms of SNHG17 in glioma still await verification. METHODS: Paired glioma samples were enrolled. SNHG17, miR-23b-3p, and zinc-fingers and homeoboxes 1 (ZHX1) mRNA expression were examined by a quantitative real-time polymerase chain reaction (qRT-PCR). SNHG17 short hairpin RNA (shRNA) and miR-23b-3p mimics were transfected into LN229 and U251 cell lines to repress SNHG17 and up-regulate miR-23b-3p expression, respectively. Proliferation, migration and invasion of LN229 and U251 cells were probed by a cell counting kit-8 assay and a Transwell assay. Bioinformatics prediction, dual-luciferase reporter assay, RNA immunoprecipitation assay, qRT-PCR and western blotting were applied to determine the regulatory relationships among SNHG17, miR-23b-3p and ZHX1. RESULTS: SNHG17 expression was markedly raised in glioma tissues, which was positively correlated with ZHX1 expression and negatively associated with the expression of miR-23b-3p. After transfection of SNHG17 shRNAs into glioma cells, the proliferation, migration and invasion of cancer cells was markedly restrained. miR-23b-3p mimics the function of SHNG17 knockdown. Furthermore, miR-23b-3p was shown to be negatively modulated by SNHG17, and ZHX1 was identified as a target of miR-23b-3p. CONCLUSIONS: SNHG17 is a "competing endogenous RNA" with respect to modulating ZHX1 expression by adsorbing miR-23b-3p and thereby promoting glioma progression.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Proteínas de Homeodomínio/metabolismo , RNA Longo não Codificante/genética , Fatores de Transcrição/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Glioma/genética , Glioma/metabolismo , Glioma/cirurgia , Proteínas de Homeodomínio/genética , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Prognóstico , Fatores de Transcrição/genética , Células Tumorais Cultivadas
15.
AAPS PharmSciTech ; 20(2): 85, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30673901

RESUMO

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease associated with the high morbidity and mortality. Long-term intermittent therapy by inhalable antibiotics has recently emerged as an effective approach for NCFB treatment. However, the effective delivery of antibiotics to the lung requires administering a high dose to the site of infection. Herein, we investigated the novel inhalable silk-based microparticles as a promising approach to deliver high-payload ciprofloxacin (CIP) for NCFB therapy. Silk fibroin (SF) was applied to improve drug-payload and deposit efficiency of the dry powder particles. Mannitol was added as a mucokinetic agent. The dry powder inhaler (DPI) formulations of CIP microparticles were evaluated in vitro in terms of the aerodynamic performance, particle size distribution, drug loading, morphology, and their solid state. The optimal formulation (highest drug loading, 80%) exhibited superior aerosolization performance in terms of fine particle fraction (45.04 ± 0.84%), emitted dose (98.10 ± 1.27%), mass median aerodynamic diameter (3.75 ± 0.03 µm), and geometric standard deviation (1.66 ± 0.10). The improved drug loading was due to the electrostatic interactions between the SF and CIP by adsorption, and the superior aerosolization efficiency would be largely attributed to the fluffy and porous cotton-like property and low-density structure of SF. The presented results indicated the novel inhalable silk-based DPI microparticles of CIP could provide a promising strategy for the treatment of NCFB.


Assuntos
Antibacterianos/administração & dosagem , Bronquiectasia/tratamento farmacológico , Ciprofloxacina/administração & dosagem , Administração por Inalação , Aerossóis , Inaladores de Pó Seco , Fibroínas , Humanos , Manitol/química , Tamanho da Partícula
16.
Entropy (Basel) ; 21(5)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33267208

RESUMO

Global optimization, especially on a large scale, is challenging to solve due to its nonlinearity and multimodality. In this paper, in order to enhance the global searching ability of the firefly algorithm (FA) inspired by bionics, a novel hybrid meta-heuristic algorithm is proposed by embedding the cross-entropy (CE) method into the firefly algorithm. With adaptive smoothing and co-evolution, the proposed method fully absorbs the ergodicity, adaptability and robustness of the cross-entropy method. The new hybrid algorithm achieves an effective balance between exploration and exploitation to avoid falling into a local optimum, enhance its global searching ability, and improve its convergence rate. The results of numeral experiments show that the new hybrid algorithm possesses more powerful global search capacity, higher optimization precision, and stronger robustness.

17.
Int J Clin Oncol ; 23(2): 389-399, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29181651

RESUMO

BACKGROUND: To evaluate the association between fatigue and anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MAbs), we conducted the first meta-analysis to access the incidence and risk of fatigue associated with anti-EGFR MAbs. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) published up to February 2017. Eligible studies were selected according to PRISMA statement. Incidence rates, risk ratio (RRs), and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Outcomes of quality were summarized in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. RESULTS: Thirty-five RCTs (including 15,622 patients) were included; median follow-up ranged from 8.1 to 71.4 months, and the fatigue events were recorded and graded according to the Common Toxicity Criteria for Adverse Events version 2.0 or 3.0 in most of the included trials. For patients receiving anti-EGFR MAbs, the overall incidence of all-grade and high-grade fatigue was 54.1% and 10.5%, respectively. Compared with control, anti-EGFR MAbs significantly increased the risk of all-grade fatigue (RR 1.10, 95% CI, 1.05-1.14, moderate-quality evidence) and high-grade fatigue (RR 1.31, 95% CI, 1.19-1.45, moderate-quality evidence). No significant differences among subgroup analyses (anti-EGFR MAbs, tumor type, and median follow-up) on high-grade fatigue were observed. No evidence of publication bias was observed. CONCLUSION: The present study suggested that anti-EGFR MAbs may increase the risk of fatigue in cancer patients.


Assuntos
Antineoplásicos/efeitos adversos , Receptores ErbB/antagonistas & inibidores , Fadiga/induzido quimicamente , Neoplasias/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/uso terapêutico , Cetuximab/efeitos adversos , Humanos , Panitumumabe , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Biol Pharm Bull ; 39(1): 97-103, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26466608

RESUMO

This paper describes the ultrasound-assisted extraction (UAE) of pristimerin from Celastrus orbiculatus. Methanol was the most effective for pristimerin extraction, followed by ethanol, ethyl acetate, n-butanol, and water. To optimize the conditions, the Box-Behnken design, a widely used form of response surface methodology, was used to investigate the effects of parameters on UAE. Several variables, such as extraction time, ultrasonic power, extraction temperature, and solvent-to-solid (S/S) ratio were investigated. The highest extraction yield of 1.843 mg/g was obtained using methanol under optimal conditions with an extraction time of 40 min, ultrasonic power of 105 W, an S/S ratio of 40 mL/g, and an extraction temperature of 52°C. The experimental values under optimal conditions agreed well with the predicted values, suggesting that UAE has good potential as an extraction method for pristimerin from C. orbiculatus.


Assuntos
Celastrus/química , Triterpenos/química , Ultrassom/métodos , Estrutura Molecular , Triterpenos Pentacíclicos , Folhas de Planta/química , Solventes
19.
Front Neurosci ; 18: 1362495, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440394

RESUMO

The clinical rehabilitation assessment methods for hemiplegic upper limb motor function are often subjective, time-consuming, and non-uniform. This study proposes an automatic rehabilitation assessment method for upper limb motor function based on posture and distributed force measurements. Azure Kinect combined with MediaPipe was used to detect upper limb and hand movements, and the array distributed flexible thin film pressure sensor was employed to measure the distributed force of hand. This allowed for the automated measurement of 30 items within the Fugl-Meyer scale. Feature information was extracted separately from the affected and healthy sides, the feature ratios or deviation were then fed into a single/multiple fuzzy logic assessment model to determine the assessment score of each item. Finally, the total score of the hemiplegic upper limb motor function assessment was derived. Experiments were performed to evaluate the motor function of the subjects' upper extremities. Bland-Altman plots of physician and system scores showed good agreement. The results of the automated assessment system were highly correlated with the clinical Fugl-Meyer total score (r = 0.99, p < 0.001). The experimental results state that this system can automatically assess the motor function of the affected upper limb by measuring the posture and force distribution.

20.
J Vis Exp ; (204)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38465928

RESUMO

Cationic nanostructures have emerged as an adjuvant and antigen delivery system that enhances dendritic cell maturation, ROS generation, and antigen uptake and then promotes antigen-specific immune responses. In recent years, retinoic acid (RA) has received increasing attention due to its effect in activating the mucosal immune response; however, in order to use RA as a mucosal adjuvant, it is necessary to solve the problem of its dissolution, loading, and delivery. Here, we describe a cationic nanoemulsion-encapsulated retinoic acid (CNE-RA) delivery system composed of the cationic lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOTAP), retinoic acid, squalene as the oil phase, polysorbate 80 as surfactant, and sorbitan trioleate 85 as co-surfactant. Its physical and chemical properties were characterized using dynamic light scattering and a spectrophotometer. Immunization of mice with the mixture of antigen (ovalbumin, OVA) and CNE-RA significantly elevated the levels of anti-OVA secretory immunoglobulin A (sIgA) in vaginal lavage fluid and the small intestinal lavage fluid of mice compared with OVA alone. This protocol describes a detailed method for the preparation, characterization, and evaluation of the adjuvant effect of CNE-RA.


Assuntos
Adjuvantes Imunológicos , Imunização , Feminino , Animais , Camundongos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Mucosa , Vacinação , Antígenos , Imunidade nas Mucosas , Tensoativos/farmacologia , Ovalbumina , Camundongos Endogâmicos BALB C
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