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Purpose: This paper presents a preliminary study on whether repetitive transcranial magnetic stimulation (rTMS) can modulate the nutritional status of persistent vegetative state (PVS) patients (the primary endpoint) by regulating the intestinal flora and the metabolites, with the correlation between them also investigated. Methods: Seventy-six patients with PVS were selected and divided into the observation group (n = 38) and the control group (n = 38) by random numerical grouping. All subjects' stool samples were examined for metabolites and analyzed regarding the short-chain fatty acids (SCFAs) content. All subjects' serum albumin, prealbumin, and hemoglobin levels were measured before and after the treatment. Nutrition risk screening 2002 was performed on all the subjects before and after the treatment and on the 30th and 90th days of the follow-up. Results: (1) Intestinal flora structure: the Chao index, Ace index, and Shannon index of the observation group and the control group were significantly higher (p < 0.05), while the Simpson index was significantly lower (p < 0.05) following the treatment. (2) Metabolites of the intestinal flora: the observation group had significantly higher levels of acetic acid, butyric acid, and valeric acid (p < 0.05), as well as lower levels of propionic acid (p < 0.05) following the treatment. (3) Nutritional status (the primary endpoint): following the treatment, the above serum nutritional indices were significantly higher in both groups (p < 0.05), while the indices of the observation group were significantly higher than those of the control group (p < 0.05). Conclusion: The rTMS method may improve the nutritional status of patients with PVS by regulating the structure of the intestinal flora and affecting the level of SCFAs through the microbiota-gut-brain axis. The possible mechanism involves how high-frequency rTMS can cause increased excitation in the frontal lobe of the right side of the brain, thus regulating the 5-hydroxytryptamine and norepinephrine levels.
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It is of great importance to treat a bacterial-infected wound by a smart dressing capable of delivering antibiotics in a smart manner without causing drug resistance. The construction of smart release nanocontainers responsive to near-infrared (NIR) laser irradiation in an on-demand and stepwise way is a promising strategy for avoiding the emergence of multidrug-resistant bacteria. Here, we develop a hydrogel composite made of alginate and nanotubes with an efficient NIR-triggered release of rifampicin and outstanding antibacterial ability. This composite hydrogel is prepared through co-encapsulating antibacterial drug (rifampicin), NIR-absorbing dye (indocyanine green), and phase-change materials (a eutectic mixture of fatty acids) into halloysite nanotubes, followed by incorporation into alginate hydrogels, allowing the in-situ gelation at room temperature and maintaining the integrity of drug-loaded nanotubes. Among them, the eutectic mixture with a melting point of 39 °C serves as the biocompatible phase-change material to facilitate the NIR-triggered drug release. The resultant phase-change material gated-nanotubes exhibit a prominent photothermal efficiency with multistep drug release under laser irradiation. In an in vitro assay, composite hydrogel provides good antibacterial potency against Staphylococcus aureus, one of the most prevalent microorganisms of dangerous gas gangrene. A bacterial-infected rat full-thickness wound model demonstrates that the NIR-responsive composite hydrogel inhibits the bacteria colonization and suppresses the inflammatory response caused by bacteria, promoting angiogenesis and collagen deposition to accelerate wound regeneration. The NIR-responsive composite hydrogel has a great potential as an antibacterial wound dressing functionalized with controlled multistep treatment of the infected sites.
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An effective synthetic method for 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition reaction has been developed. This reaction could smoothly proceed between ninhydrin-derived Morita-Baylis-Hillman carbonates and nitrilimines to provide a wide scope of differently substituted pyrazoles in high yields (up to 95%). In addition, the reaction mechanism was also proposed to explain its regioselectivity.
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Iminas , Ninhidrina , Carbonatos , Catálisis , Reacción de Cicloadición , Nitrilos , PirazolesRESUMEN
To advance the structural development and fully explore the application potential, it is highly desirable but challenging to elucidate the relationship between the structures and properties of ZnII-LnIII heterometallic species. Herein, three types of ZnII-LnIII heterometallic compounds (LnIII = GdIII, TbIII) formulated as [Zn16Ln4L12(µ3-O)4(NO3)12]·8CH3CN (ZnLn-1), [Zn2Ln2L2(NO3)6(H2O)2]·3CH3CN (ZnLn-2), and [Zn4Ln2L8(OAc)12]·xCH3CN (ZnLn-3: for Ln = Gd, x = 5; for Ln = Tb, x = 4) were dictated by common inorganic anions, NO3- and OAc-, with the aid of the multidentate ligand H2L with propane as the central skeleton and 3-methoxysalicylamide and 3-methoxysalicylaldimine as terminal groups. ZnLn-1 features cubic cages with four {Zn4L3} tetrahedral subunits and four Ln3+ centers positioned at the eight vertices alternately when NO3- was introduced into the reaction system exclusively. An attempt to replace NO3- in ZnLn-1 with OAc- partially led to the formation of {Zn2Ln2L2} heterometallic wheels. Meanwhile, ZnLn-3 featuring double-hairpin-like {Zn4Ln2L4} hemicycles that are orthogonal to each other assisted by intermolecular hydrogen bonds was constructed when NO3- in ZnLn-1 was completely replaced by OAc-. Their structural integrity in solution were ascertained by both emission and 1H NMR spectroscopy. Ascribed to the different Zn2+-containing antenna, ZnTb-2 possesses a relatively strong emission characteristic of Tb3+; ZnTb-1 has moderate Tb3+ luminescence, yet an absence of Tb3+ emission is found in ZnTb-3. Such an emission difference could be mainly attributed to the antenna effect directed by distinct structural characteristics induced by anions. The anion-dictated self-assembly strategy presented herein not only offers a facile approach to regulate the coordination mode of H2L to such an extent to obtain diverse structures of ZnII-LnIII heterometallic species but also provides an understanding of how common inorganic anions tune coordination-driven self-assemblies as well as the subsequent luminescence properties.
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From the perspective of human health and environmental safety, the development of hydrostable fluorescent sensors for the detection of heavy metal ions and nitroaromatics is an important but a challenging issue. To this end, a water-stable Zn2+ coordination polymer formulated as {[Zn(H2L)]·2DMF·3H2O}n (ZnCP) was prepared elaborately by a solvothermal method using a multidentate ligand (H4L) with 2,6-pyridine-dicarboxylic acid spaced by para-substituted benzene. Single-crystal analysis shows that the new ZnCP exhibits one-dimensional chain structural features, which further promoted to afford a wrinkled two-dimensional network structure via inter-chain hydrogen bonding. Powder X-ray diffraction and fluorescence measurements show that it can maintain crystallinity and structural integrity under harsh acidic and alkaline conditions with the pH ranging from 4 to 11. Notably, the bright blue-emissive ZnCP showed selective fluorescence quenching effects for Fe3+ and picric acid (PA), which makes it an excellent chemical sensor for Fe3+ and picric acid (PA) with low detection limits of 0.41 and 0.26 µM in water. The recognition mechanism of Fe3+ could be attributed to UV absorption competition and resonance energy transfer in the aid of weak electrostatic interactions, while the recognition mechanism of PA is considered to be a multi-quenching mechanism dominated by absorption competition and PET effects with the assistance of hydrogen bonding. In addition, poly(methyl methacrylate) (PMMA) films doped with ZnCP (ZnCP@PMMA) were developed to provide better sensing performance and portability for practical applications.
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Bidirectional regulation is one of the key function of acupuncture. The stimulator, mediator and receptor are the basis while the specificity of acupoints and the multi-target regulation of receptors receiving stimulation signals are the essential link of the bidirectional regulation of acupuncture. The possible mechanisms of bidirectional regulation of acupuncture are discussed in 4 aspects, i.e. homeostasis mechanism, stress reaction, central adaptive regulation and autonomic nerve regulation. Knowing the limitations of bidirectional regulation and exploring suitable researchmethods are proposed to be the key points in future researches.
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Terapia por Acupuntura , Acupuntura , Puntos de AcupunturaRESUMEN
BACKGROUND: Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests. METHODS: We conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis. RESULTS: In this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P < 0.001). The odds ratio for having asthma increased progressively with a gradual increase in FeNO or B-Eos count (both P < 0.001; assessed using the Cochran-Armitage trend test). Further analysis of in-series combinations of different threshold values for these biomarkers indicated that moderately elevated biomarker levels (FeNO > 40 ppb and B-Eos > 300 cells/µl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017-2019 data as the internal validation dataset. CONCLUSION: FeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/µl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible.
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Asma/diagnóstico , Eosinófilos , Prueba de Óxido Nítrico Exhalado Fraccionado , Adulto , Asma/sangre , Asma/complicaciones , Estudios de Cohortes , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Eosinofilia Pulmonar/complicaciones , Estudios RetrospectivosRESUMEN
OBJECTIVE: This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm. METHODS: A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for 1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated. RESULTS: The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (pâ<â0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in observation group were significantly reduced compared to those in control group (pâ<â0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (pâ<â0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (pâ<â0.05), but negatively correlated with changes in NO (pâ<â0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (pâ<â0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (pâ<â0.05), and there were no significant differences of adverse reactions between the two groups (pâ>â0.05). CONCLUSION: For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body's aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy.
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Antihipertensivos/uso terapéutico , Betahistina/uso terapéutico , Proteína C-Reactiva/efectos de los fármacos , Citocinas/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Nimodipina/uso terapéutico , Vasodilatadores/uso terapéutico , Vasoespasmo Intracraneal/tratamiento farmacológico , Anciano , Antihipertensivos/farmacología , Betahistina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nimodipina/administración & dosificación , Vasodilatadores/farmacologíaRESUMEN
Long non-coding RNAs (lncRNAs) have been investigated as a novel class of regulators of cellular processes, including cell growth, apoptosis and carcinogenesis. lncRNA BRAF-activated non-protein coding RNA (BANCR) has recently been revealed to be involved in tumorigenesis of numerous types of cancer, including papillary thyroid carcinoma, melanoma, non-small cell lung cancer and colorectal cancer. However, the expression profiles and biological relevance of lncRNA BANCR in hepatocellular carcinoma (HCC) has not yet been reported. In the present study, the expression level of BANCR in tumor tissues and para-cancerous tissues was determined by reverse transcription-quantitative polymerase chain reaction in patients with hepatitis B virus (HBV)-associated HCC, and its association with clinicopathological characteristics of patients was analyzed. The results demonstrated that the expression level of BANCR was significantly reduced in tumor tissues in comparison with in para-cancerous tissues (P<0.001). Furthermore, the present study demonstrated that BANCR expression level was closely associated with serum α-fetoprotein levels (P<0.01) and HCC tumor number (P<0.05). To the best of our knowledge, these results revealed for the first time that BANCR downregulated in patients with HBV-associated HCC and BANCR expression level may be a potential valuable diagnosis and therapeutic biomarker in HCC.
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Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. Despite progress in the diagnosis and treatment of HCC, prognosis remains unfavorable. Long non-coding RNAs (lncRNAs) are emerging as important factors in tumorigenesis and cancer progression; however, the underlying molecular mechanisms and clinical significance of lncRNAs in HCC remain largely unknown. The present study examined the expression pattern and clinical significance of a novel lncRNA, LOC728290, in HCC. Expression of LOC728290 was markedly decreased in HCC tissues compared with adjacent non-tumor liver tissues, as detected using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The area under the receiver operating characteristic curve for LOC728290 was 0.728. The expression of LOC728290 was associated with the level of α-fetoprotein and microvascular invasion. Furthermore, patients with low LOC728290 expression exhibited decreased recurrence-free survival times (P<0.05) compared with those with high LOC728290 expression. The results of the present study indicated that downregulation of LOC728290 in patients with HCC may be a powerful tumor biomarker, with potential clinical applications in prognosis as well as a therapeutic target.
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The present report describes a case of diffuse panbronchiolitis (DPB) in a child from Western China and the favorable outcome associated with early diagnosis. DPB is an uncommon presentation in pediatric patients. A 13-year-old Chinese boy was admitted to the respiratory outpatient department due to recurrent cough and progressive exertional dyspnea that had persisted for 1 year. An initial diagnosis of bronchial asthma was made, and the patient was prescribed inhaled fluticasone combined with salmeterol (50/250 µg, twice daily), and montelukast (4 mg daily). However, 2 months later no clinical improvement was observed. The disease was re-diagnosed as DPB following the identification of features such as centrilobular small nodular opacities, a 'tree-in-bud appearance' and thickening of the bronchial walls meeting the diagnostic criteria for DPB. Complete resolution of the disease and sustained alleviation of the patient's respiratory symptoms were achieved following the early institution of erythromycin therapy, and the exacerbation of chronic bronchitis was reduced. In conclusion, it is essential to consider that successful treatment for DPB lies in early diagnosis and early treatment. DPB may be treated well by use of erythromycin.
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Bovine aortic endothelial cells (BAECs) were cultured with high glucose (33 mmol/L), 4 mg/L green tea polyphenols (GTPs) or 4 mg/L GTPs co-treatment with high glucose for 24 h in the presence or absence of Bafilomycin-A1 (BAF). We observed that high glucose increased the accumulation of LC3-II. Treatment with BAF did not further increase the accumulation of LC3-II. Results also showed an increased level of p62 and decreased Beclin-1. However, GTPs showed inversed trends of those proteins. Furthermore, GTPs co-treatment with high glucose decreased the level of LC3-II and a much higher accumulation of LC3-II was observed in the presence of BAF in comparison with high glucose alone. Results also showed a decreased p62 and increased Beclin-1. The results demonstrated that GTPs alleviated autophagy inhibition induced by high glucose, which may be involved in the endothelial protective effects of green tea against hyperglycemia.
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Autofagia/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Glucosa/toxicidad , Polifenoles/farmacología , Té/química , Animales , Bovinos , Células Cultivadas , Células Endoteliales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Macrólidos/farmacología , Polifenoles/químicaRESUMEN
Coronary artery heart disease (CHD) is one of the common cardiovascular diseases in clinical. The morbidity and mortality of CHD recently continue increasing in our country, which has aroused wide attention. Many studies confirm that traditional Chinese medicine has better therapeutic effect on CHD. Guanxin Danshen formula, widely used in the treatment of CHD, consists of Salviae Miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and volatile oil from Dalbergiae Odoriferae Lignum, and has the efficacy in promoting blood circulation to resolve stasis, regulating the circulation of Qi and alleviating pain. This review summarized the pharmacologic effects and mechanism of Guanxin Danshen formula and its effective components in the treatment of CHD to provide reference for its fundamental research and clinical application.
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Medicamentos Herbarios Chinos/farmacología , Cardiopatías/tratamiento farmacológico , Vasos Coronarios/fisiopatología , Humanos , Medicina Tradicional China , Rizoma , Salvia miltiorrhizaRESUMEN
Epigenetic is a hotspot of post-genomic era research, and epigenetic modification is a mechanism in the study of cardiovascular disease. Myocardial ischemia-reperfusion injury (MIRI) is one of the problems in the cardiovascular disease, and many experimental interventions are reported in the protection of the ischemic myocardium in experimental animals. However, with the exception of early reperfusion, none has been translated into clinical practice. There is an advantage of traditional Chinese medicine (TCM) in the regulation of epigenetic modification, and pathogenesis of myocardial ischemia-reperfusion injury. This review article is prepared to cover the research progress in the treatment of myocardial ischemia-reperfusion injury by TCM with a focus on epigenetic regulation. The epigenetic regulation is documented in TCM theory through a systematic review of the protecting drugs in the MIRI development guidelines.
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Epigénesis Genética , Medicina Tradicional China , Daño por Reperfusión Miocárdica/terapia , Animales , Sustancias Protectoras/farmacologíaRESUMEN
Owing to their unique properties such as low cytotoxicity and excellent biocompatibility, poly(aspartic acid) (PAsp) and polysaccharides are good candidates for the development of new biomaterials. In order to construct better gene delivery systems by combining polysaccharides with PAsp, in this work, a general strategy is described for preparing series of polysaccharide-graft-PAsp (including cyclodextrin (CD), dextran (Dex) and chitosan (CS)) gene vectors. Such different polysaccharide-based vectors are compared systematically through a series of experiments including degradability, pDNA condensation capability, cytotoxicity and gene transfection ability. They possess good degradability, which would benefit the release of pDNA from the complexes. They exhibit significantly lower cytotoxicity than the control 'gold-standard' polyethylenimine (PEI, â¼25kDa). More importantly, the gene transfection efficiency of Dex- and CS-based vectors is 12-14-fold higher than CD-based ones. This present study indicates that properly grafting degradable PAsp from polysaccharide backbones is an effective means of producing a new class of degradable biomaterials.
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Vectores Genéticos , Péptidos/química , Polisacáridos/química , Transfección , Células Hep G2 , HumanosRESUMEN
The development of new cationic nanoparticles that are safe and effective for biomedical applications has attracted considerable attention. Low molecular weight polycations generally exhibit low toxicity; however, their poor efficiency in drug delivery systems hampers their application. In this work, a series of new low molecular weight 2,6-bis(1-methylbenzimidazolyl)pyridinyl (BIP)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s (BIP-PGEAs) were readily fabricated for effective codelivery of a gene and a drug. The BIP-PGEAs could form well-defined cationic nanoparticles (NPs) in an aqueous solution. They could effectively bind pDNA with an appropriate particle size and ζ-potential. More importantly, the BIP-PGEA NPs demonstrated much higher transfection efficiencies than linear PGEA (L-PGEA) and the traditional "gold-standard" branched polyethylenimine (25 kDa). Moreover, the BIP-PGEA NPs could effectively entrap a hydrophobic anticancer drug such as 10-hydroxy camptothecin (CPT). The synergistic antitumor effect of the BIP-PGEA-CPT NPs was demonstrated by employing a suicide gene therapy system, which contained cytosine deaminase and 5-fluorocytosine (CD/5-FC). The present strategy for preparing well-defined cationic nanoparticles from low-molecular-weight polycations could provide an intriguing method to produce new multifunctional, therapeutic NPs.
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ADN/metabolismo , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Nanopartículas/química , Plásmidos/metabolismo , Poliaminas/química , Animales , Antineoplásicos/farmacología , Células COS , Camptotecina/farmacología , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Proteínas Fluorescentes Verdes/metabolismo , Células Hep G2 , Humanos , Peso Molecular , Nanopartículas/ultraestructura , Tamaño de la Partícula , Polielectrolitos , Ácidos Polimetacrílicos/síntesis química , Ácidos Polimetacrílicos/química , Piridinas/síntesis química , Piridinas/química , Espectrofotometría Ultravioleta , Electricidad Estática , TransfecciónRESUMEN
The Chinese surf clam Mactra chinensis Philippi, 1846 is a commercially important marine bivalve belonging to the family Mactridae (Mollusca: Bivalvia). In this study, the M. chinensis mitochondrial genomic features are analyzed. The genome has 34 genes on the same strand, lacking atp8 and both trnS (trnS1 and trnS2) as compared with the typical gene content of metazoan mitochondrial genomes. The A+T content of M. chinensis mitochondrial genome is 63.72%, which is slightly lower than that of M. veneriformis (67.59%) and Coelomactra antiquata (64.33% and 64.14% for the samples from Ri Zhao, Shandong Province, and Zhang Zhou, Fujian Province, China, respectively) in the same family. There are 22 NCRs in the M. chinensis mitochondrial genome, accounting for 12.91% of the genome length. The longest NCR (1,075bp in length) is located between trnT and trnQ. A TRS (127bp×8.15) accounts for 96.3% (1,035/1,075) of this NCR. The occurrence of TRS in NCR is shared by the two Mactra mitochondrial genomes, but is not found in the two Coelomactra mitochondrial genomes. A phylogenetic tree constructed based on 12 PCGs of 25 bivalve mitochondrial genomes shows that all seven genera (Mactra, Coelomactra, Paphia, Meretrix, Solen, Mytilus, and Crassostrea) constitute monophyletic groups with very high support values. Pairwise genetic distance analyses indicate that the genetic distance of C. antiquata from the two localities is 0.084, which is greater than values between congeneric species, such as those in Mactra, Mytilus, Meretrix, and Crassostrea. The results show that the C. antiquata from the two localities represent cryptic species.
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Bivalvos/genética , Genoma Mitocondrial , Animales , Bivalvos/citología , ADN Mitocondrial/genética , Orden Génico , Filogenia , ARN Ribosómico/genéticaRESUMEN
Pullulan due to its specificity for liver has been widely exploited for biomedical applications. In this work, a tailor-made biocleavable pullulan-based gene vector (PuPGEA) with good hemocompatibility was successfully proposed via atom transfer radical polymerization (ATRP) for efficient liver cell-targeting gene delivery. A two-step method involving the reaction of hydroxyl groups of pullulan with cystamine was developed to introduce reduction-sensitive disulfide-linked initiation sites of ATRP onto pullulan. The poly(glycidyl methacrylate) (PGMA) side chains prepared subsequently via ATRP were functionalized with ethanolamine (EA) to produce the resultant biocleavable comb-shaped PuPGEA vectors consisting of nonionic pullulan backbones and disulfide-linked cationic EA-functionalized PGMA (PGEA) side chains with plentiful secondary amine and nonionic hydroxyl units. The cationic PGEA side chains can be readily cleavable from the pullulan backbones of PuPGEA under reducible conditions. Due to the liver targeting performance of pullulan backbones, such PuPGEA vectors exhibited much higher gene transfection efficiency and cellular uptake rates in HepG2 cell lines than in Hella cell lines. In addition, in vitro transfection efficiency and uptake mechanism of polyplex in HepG2 cells were evaluated in the presence of different endocytosis inhibitors, indicating that the asialoglycoprotein receptor was involved in transfection process of hepatocytes. More importantly, in comparison with gold standard polyethylenimine (PEI, â¼25 kDa), PuPGEA vectors possessed excellent hemocompatibility without causing undesirable hemolysis. Properly grafting short bioreducible PGEA polycation side chains from a liver cell-targeting pullulan backbone is an effective means to produce new hemocompatible polysaccharide-based gene delivery vectors.
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Técnicas de Transferencia de Gen , Vectores Genéticos , Glucanos/química , Hígado , Endocitosis/efectos de los fármacos , Hemólisis/efectos de los fármacos , HumanosRESUMEN
In our screening program for insecticidal activity of the essential oils/extracts derived from some Chinese medicinal herbs and spices, garlic (Allium sativum L.) essential oil was found to possess strong insecticidal activity against overwintering adults of Cacopsylla chinensis Yang et Li (Hemiptera: Psyllidae). The commercial essential oil of A. sativum was analyzed by gas chromatography-mass spectrometry. Sixteen compounds, accounting for 97.44% of the total oil, were identified, and the main components of the essential oil of A. sativum were diallyl trisulfide (50.43%), diallyl disulfide (25.30%), diallyl sulfide (6.25%), diallyl tetrasulfide (4.03%), 1,2-dithiolane (3.12%), allyl methyl disulfide (3.07%), 1,3-dithiane (2.12%), and allyl methyl trisulfide (2.08%). The essential oil of A. sativum possessed contact toxicity against overwintering C. chinensis, with an LC50 value of 1.42 microg per adult. The two main constituent compounds, diallyl trisulfide and diallyl disulfide, exhibited strong acute toxicity against the overwintering C. chinensis, with LC50 values of 0.64 and 11.04 /g per adult, respectively.
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Allium/química , Compuestos Alílicos/farmacología , Hemípteros/efectos de los fármacos , Insecticidas/farmacología , Aceites Volátiles/farmacología , Sulfuros/farmacología , Animales , Relación Dosis-Respuesta a Droga , Cromatografía de Gases y Espectrometría de Masas , Dosificación Letal MedianaRESUMEN
For ideal polymeric gene vectors, their serum stability is of crucial importance. Polycation vectors usually suffer from colloidal aggregation, which makes them easily cleared from the bloodstream. Recently, we reported a comb-shaped vector (DPD) consisting of a dextran backbone and disulfide-linked cationic poly((2-dimethyl amino)ethyl methacrylate) side chains for efficient gene delivery. In this work, versatile functionalization of DPD (as a model gene vector) was proposed via the introduction of different types of zwitterionic carboxybetaine and sulfobetaine species for improving biophysical properties. The incorporation of zwitterionic betaine did not destroy the DNA condensation capability of vectors. All the zwitterionic betaine-functionalized DPD vectors exhibited lower cytotoxicities than the pristine DPD. The DPD-b-polycarboxybetaine block copolymer (DPDbPC) exhibited better gene delivery abilities than the corresponding DPD-r-polycarboxybetaine random copolymer (DPDrPC). Moreover, in the serum case with a high concentration (30%) of fetal bovine serum, the DPD-b-polysulfobetaine block copolymer (DPDbPS) produced much higher gene transfection efficiencies than DPDbPC. Cellular internalization results indicated that the incorporation of zwitterionic betaine could benefit serum stabilities of vectors and enhance cellular uptake. The present study demonstrated that proper incorporation of zwitterionic betaine into gene carriers was an effective method to produce serum-tolerant transfection vectors.