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1.
Methods Mol Biol ; 2057: 103-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31595474

RESUMO

Nitrogen (N2) is the most necessary element in the atmosphere, it is an energetic micronutrient for plant growth and development after water, besides its key role in chlorophyll production, which is crucial for photosynthesis process. Biological nitrogen fixation is measured to be the most potent method to deliver a fixed way of nitrogen to the plants. Plant depends on free-living and symbiotic microbes present in the soil for nitrogen because it cannot be absorbed by the plant itself directly from the atmosphere. Many techniques were reported in the laboratory for nitrogen estimation till now, but Kjeldahl digestion and acetylene reduction assay (ARA) techniques became the most popular. In this chapter, we focus on the most common and popular methods used to determine plant N2; awareness obtained through the wide application of these methods should offer the source for the N2 fixation rate in agriculture system.

2.
J Nanosci Nanotechnol ; 20(2): 1008-1012, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383098

RESUMO

Institute of Materials, Chinese Academy of Engineering Physics, Jiangyou 621908, P. R. China To improve the stability of organic-inorganic hybrid perovskite, cesium-containing methylammonium lead iodide perovskite have been synthesized by one-step solution deposition. With the increasing of Cs+ doping concentration, direct optical band gap of perovskite was increases, while defects and roughness of perovskite thin films were gradually augmented. A certain amount of Cs+ incorporated in perovskite absorb layer could improve power conversion efficiency through the enhancing of open circuit voltage and fill factor. However, excessive Cs+ doping concentration results in the reduced of short-circuit current and fill factor, which reduced power conversion efficiency. The optimized ratio 10% Cs+ doping achieved the highest power conversion efficiency (16.84%).

3.
J Chromatogr A ; : 460624, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31668866

RESUMO

ß-agonists, which have been illegally used in animal production in some countries, can induce bioaccumulation when blood is converted by rendering into blood meal. Unfortunately, available data on this topic are scarce, which result in lack of risk assessment. Therefore, in this research, a method for simultaneous determination of 22 ß-agonists in blood meal by liquid chromatography coupled with tandem mass spectrometry using isotope dilution was developed. The recoveries of the developed method ranged from 68.6% to 118.8% with RSD at below 20%. the limit of detection (LOD) is blew 1 µg/kg. The change in agonist form added and incurred blood into blood meal and long stability of ß-agonist in blood meal were studied. Then, we analyzed blood meal for 22 agonists using this method. The results suggest blood meal is a possible pathway for agonist reentry into animals. Potential risks of agonist residues in blood meal were examined. This study is the first to explore source of ß-agonist residues in blood meal, change in processing produce and stability in stored stage.

4.
Dev Comp Immunol ; : 103529, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669309

RESUMO

The myeloid differentiation protein 2 (MD2)-related lipid-recognition (ML) proteins display diverse biological functions in host immunity and lipid metabolism by interacting with different lipids. Human MD2, an indispensable accessory protein in TLR4 signaling pathway, specifically recognizes lipopolysaccharides (LPS), thereby leading to the activation of TLR4 signaling pathway to produce many effectors that participate in inflammatory and immune responses against Gram-negative bacteria. Toll and immune deficiency (IMD) pathways are first characterized in Drosophila and are reportedly present in crustaceans, but the recognition and activation mechanism of these signaling pathways in crustaceans remains unclear. In the present study, a novel ML protein was characterized in mud crab (Scylla paramamosain) and designated as SpMD2. The complete SpMD2 cDNA sequence is 1114 bp long with a 465 bp open reading frame; it encodes a protein that contains 154 amino acids (aa). In the deduced protein, a signal peptide (1-21 aa residues) and a ML domain (43-151 aa residues) were predicted. SpMD2 shared a similar three-dimensional structure and a close evolutionary relationship with human MD2. SpMD2 was highly expressed in gills, hemocytes, intestine, and hepatopancreas and was upregulated in gills and hemocytes after challenges with bacteria, thereby suggesting its involvement in antibacterial defense. Western blot assay showed that SpMD2 possesses strong binding activities to different bacteria and two fungi. ELISA demonstrated that SpMD2 exhibits binding abilities to LPS, lipid A, peptidoglycan (PGN), and lipoteichoic acid (LTA). Its binding ability to LPS and lipid A were stronger than to PGN or LTA, implying that SpMD2 was an important LPS-binding protein in mud crab. Bacterial clearance assay revealed that the pre-incubation of Vibrio parahemolyticus with SpMD2 facilitates bacterial clearance in vivo and that knockdown of SpMD2 dramatically suppresses the bacterial clearance and decreases the expression of several antimicrobial peptides (AMPs). Furthermore, SpMD2 overexpression could enhance the promoter activity of SpALF2. These results revealed that SpMD2 affects bacterial clearance by regulating AMPs. Thus, by binding to LPS and by regulating AMPs, SpMD2 may function as a potential receptor, which is involved in the recognition and activation of a certain immune signaling pathway against Gram-negative bacteria. This study provides new insights into the diverse functions of ML proteins and into the antibacterial mechanisms of crustaceans.

5.
JAMA Oncol ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580391

RESUMO

Importance: Moving to multigene testing for all women with breast cancer (BC) could identify many more mutation carriers who can benefit from precision prevention. However, the cost-effectiveness of this approach remains unaddressed. Objective: To estimate incremental lifetime effects, costs, and cost-effectiveness of multigene testing of all patients with BC compared with the current practice of genetic testing (BRCA) based on family history (FH) or clinical criteria. Design, Setting, and Participants: This cost-effectiveness microsimulation modeling study compared lifetime costs and effects of high-risk BRCA1/BRCA2/PALB2 (multigene) testing of all unselected patients with BC (strategy A) with BRCA1/BRCA2 testing based on FH or clinical criteria (strategy B) in United Kingdom (UK) and US populations. Data were obtained from 11 836 patients in population-based BC cohorts (regardless of FH) recruited to 4 large research studies. Data were collected and analyzed from January 1, 2018, through June 8, 2019. The time horizon is lifetime. Payer and societal perspectives are presented. Probabilistic and 1-way sensitivity analyses evaluate model uncertainty. Interventions: In strategy A, all women with BC underwent BRCA1/BRCA2/PALB2 testing. In strategy B, only women with BC fulfilling FH or clinical criteria underwent BRCA testing. Affected BRCA/PALB2 carriers could undertake contralateral preventive mastectomy; BRCA carriers could choose risk-reducing salpingo-oophorectomy (RRSO). Relatives of mutation carriers underwent cascade testing. Unaffected relative carriers could undergo magnetic resonance imaging or mammography screening, chemoprevention, or risk-reducing mastectomy for BC risk and RRSO for ovarian cancer (OC) risk. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained and compared with standard £30 000/QALY and $100 000/QALY UK and US thresholds, respectively. Incidence of OC, BC, excess deaths due to heart disease, and the overall population effects were estimated. Results: BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC annually would cost £10 464/QALY (payer perspective) or £7216/QALY (societal perspective) in the United Kingdom or $65 661/QALY (payer perspective) or $61 618/QALY (societal perspective) in the United States compared with current BRCA testing based on clinical criteria or FH. This is well below UK and US cost-effectiveness thresholds. In probabilistic sensitivity analysis, unselected multigene testing remained cost-effective for 98% to 99% of UK and 64% to 68% of US health system simulations. One year's unselected multigene testing could prevent 2101 cases of BC and OC and 633 deaths in the United Kingdom and 9733 cases of BC and OC and 2406 deaths in the United States. Correspondingly, 8 excess deaths due to heart disease occurred in the United Kingdom and 35 in the United States annually. Conclusions and Relevance: This study found unselected, high-risk multigene testing for all patients with BC to be extremely cost-effective compared with testing based on FH or clinical criteria for UK and US health systems. These findings support changing current policy to expand genetic testing to all women with BC.

6.
Int J Chron Obstruct Pulmon Dis ; 14: 2319-2329, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632001

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is recognized as a chronic lung disease with incomplete reversible airflow limitation, but its pathophysiology was still not clear. This study aimed at investigating regulatory roles of special miRNA-mRNA axis in COPD development. Methods: Differentially expressed miRNAs and downstream mRNAs were screened from the Gene Expression Omnibus (GEO) dataset by using the LIMMA package in R software. Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct a co-expression network for COPD. The correlation of dysregulated miRNA(s) and COPD was analyzed, and miRNAs with significant differences were validated in peripheral blood mononuclear cells (PBMCs) from COPD patients by real-time PCR. Regulatory roles of candidate miRNAs and targeted mRNAs were investigated in vitro study. Results: Thirteen modules of co-expressed miRNAs and mRNAs were constructed from a selected cohort with WGCNA. Turquoise module with 12 differentially expressed miRNAs and 120 mRNAs was significantly correlated with COPD. The expression of hsa-miR-664a-3p, an upregulated miRNA in the module, was increased both in lung tissue and PBMCs from COPD patients, whereas that targeted four and a half LIM domains 1 (FHL1) gene was decreased and positively correlated with forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC%) (r = 0.59, p < 0.01). In vitro, luciferase activity assay revealed FHL1 as a target of hsa-miR-664a-3p and it could be directly downregulated by overexpression of hsa-miR-664a-3p. Furthermore, cigarette smoke extract could increase hsa-miR-664a-3p level and decrease FHL1 level in Beas-2B cells. Conclusion: The present study validated significant upregulation of hsa-miR-664a-3p in COPD patients, and its target gene FHL1 was downregulated and positively correlated with FEV1/FVC%; both hsa-miR-664a-3p and FHL1 could be regulated by cigarette smoke extract. Results of bioinformatic analyses and expanded validation suggest that the axis from hsa-miR-664a-3p to FHL1 might play a key role in cigarette smoke-induced COPD, and the exact mechanism should be confirmed in further studies.

7.
Magn Reson Imaging ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654738

RESUMO

Atheroembolic renal disease (AERD) is the major cause of renal insufficiency in the elderly, and particularly, the diagnose of AERD is often delayed and even missed due to its nonspecific presentation and the sudden occurrence of an embolic event. To investigate the feasibility of the view-shared compressed sensing (VCS) based dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in the assessment of AERD in animal models. The reproducibility of VCS DCE-MRI based glomerular filtration rate (GFR) estimation was first evaluated using the three healthy rabbits. Animal models of unilateral AERD were then conducted. All the rabbits underwent VCS DCE-MRI and the GFR maps were estimated by a commonly used cortical-compartment model. The whole kidney and suspicious lesion region GFR values of embolized kidneys were then compared with the corresponding values of normal kidneys. Finally, the suspicious lesion regions were confirmed by the corresponding renal specimens and histological findings. The reproducibility of GFR measurements was analyzed using the coefficient of variation and Bland-Altman analysis. The GFR values of normal and embolized kidneys were compared using the Student t-test. Contrast-enhanced images with sufficient diagnostic quality and reduced motion artifacts are obtained at a temporal resolution of 2.5 s. The Bland-Altman plot indicated close agreement between the GFR values estimated from between-day scans in healthy rabbits. Besides, there existed significant differences between the pixel-wise GFR values of normal and AERD kidneys in region-based comparison(P < 0.0001). The suspicious lesions are consistent well with the renal specimen and histological findings. The preliminary animal study verified the feasibility of VCS DCE-MRI for renal function evaluation, and the strategy could potentially provide a valuable tool to identify AERD.

8.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3645-3652, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602936

RESUMO

Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.


Assuntos
Biofarmácia , Absorção Intestinal , Humanos , Intestinos/efeitos dos fármacos , Medicina Tradicional Chinesa , Perfusão , Permeabilidade
9.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3653-3661, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602937

RESUMO

For the effects of multi-component environment on the solubility and permeability of single components,and the problems of biopharmaceutical attribute classification of single components in the compound prescriptions environment,baicalein was used as the research object in this study to investigate the biopharmaceutic attributes of single-component and their traditional Chinese medicine( TCM) biopharmaceutic attributes in the multi-component environment of Gegen Qilian Decoction. Shaking flask method,intrinsic dissolution rate test and HPLC were used to determine solubility of baicalein. Markers specified by FDA were utilized as permeable boundary reference materials to verify the applicability of the single-pass intestinal perfusion method( SPIP),and the quantitative research on the permeability of baicalein was also conducted. It is concluded that baicalein could be categorized as BCS-Ⅱ drug based on its low solubility and high intestinal permeability values,and it may be categorized into CMMBCS-I in the multi-component environment of Gegen Qilian Decoction due to its poor solubility but enhanced solubility and permeability in compound environment. This study could provide verification ideas for clinical determination of the best human oral dose of baicalein,and provide the data basis for the study of biopharmaceutics classification system of Chinese materia medica( CMMBCS).


Assuntos
Biofarmácia/classificação , Medicamentos de Ervas Chinesas/química , Flavanonas/química , Materia Medica/classificação , Humanos , Absorção Intestinal , Permeabilidade , Solubilidade
10.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3411-3418, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31621227

RESUMO

To explore the distribution of fungal community in soil of brown coniferous forest in Daxing'anling and its relationship with soil characteristics, soil fungal community structure and diversity in three forest types, light brown coniferous forest, grass brown coniferous forest, and typical brown coniferous forest, were analyzed by high-throughput sequencing technology. The relationship between soil fungal community and soil characteristics was analyzed by R and SPSS 17.0 software. The results showed that soil physical and chemical characteristics differed significantly across the three brown coniferous forests. A total of 111 species belonged to six phyla, 23 class, 46 orders, 74 families and 88 genera were recorded in this study. Ascomycetes and basidiomycetes were dominant phyla. There were significant differences in relative abundance of phyla among three forest types. There was no significant difference in the Ace and Chao1 diversity indices among three brown coniferous forests, whereas there were significant differences in the Shannon and Simpson indices. Results from canonical correlation analysis and correlation analysis showed that both α and ß diversity were significantly correlated with soil moisture, soil pH, soil organic matter, soil total nitrogen, and soil total potassium. The results indicated that soil characteristics were important factors affecting soil fungal diversity of brown coniferous forest in Xing'an larch forest in Daxing'anling.


Assuntos
Coniferophyta , Solo , China , Florestas , Fungos
11.
BMC Complement Altern Med ; 19(1): 271, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31627724

RESUMO

BACKGROUND: Plant secondary metabolites and phytochemicals that exhibit strong bioactivities have potential to be developed as safe and efficient natural antimicrobials against food contamination and addressing antimicrobial resistance caused by the overuse of chemical synthetic preservative. In this study, the chemical composition, antibacterial activities and related mechanism of the extracts of the valonia and the shell of Quercus variabilis Blume were studied to determine its potential as a safe and efficient natural antimicrobial. METHODS: The phenolic compositions of valonia and shell extracts were determined by folin-ciocalteau colourimetric method, sodium borohydride/chloranil-based assay and the aluminium chloride method and then further identified by the reverse-phase HPLC analysis. The antibacterial activities of valonia and shell extracts were evaluated by the agar disk diffusion method and agar dilution method. The related antibacterial mechanism was explored successively by the membrane of pathogens effect, phosphorous metabolism, whole-cell proteins and the microbial morphology under scanning electron microscopy. RESULTS: The n-butanol fraction and water fraction of valonia along with n-butanol fraction of the shell contains enrich phenolics including ellagic acid, theophylline, caffeic acid and tannin acid. The n-butanol fraction and ethanol crude extracts of valonia exhibited strong antibacterial activities against Salmonella paratyphi A (S. paratyphi A) and Staphylococcus aureus (S. aureus) with the DIZ values ranged from 10.89 ± 0.12 to 15.92 ± 0.44, which were greater than that of the Punica granatum (DIZ: 10.22 ± 0.18 and 10.30 ± 0.21). The MIC values of the n-butanol fraction and ethanol crude extracts of valonia against S. paratyphi A and S. aureus were 1.25 mg/ml and 0.625 mg/ml. The related antibacterial mechanism of n-butanol fraction and ethanol crude extracts of valonia may be attributed to their strong impact on membrane permeability and cellular metabolism. Those extracts exhibited strong antibacterial activity according to inhibit the synthesis of bacterial proteins and seriously change morphological structure of bacterial cells. CONCLUSIONS: The n-butanol fraction and ethanol crude extracts of valonia had reasonably good antibacterial activities against S. paratyphi A and S. aureus. This study suggests possible application of valonia and shell as natural antimicrobials or preservatives for food and medical application.

12.
Medicine (Baltimore) ; 98(40): e17244, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577716

RESUMO

RATIONALE: Gitelman syndrome (GS) is a rare autosomal recessive hereditary salt-losing tubulopathy caused by loss-of-function mutations in the SLC12A3 gene. It is usually characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. There are only a few reports on GS combined with growth hormone deficiency (GHD). PATIENT CONCERNS: Three patients presented with weakness, spasm, and growth retardation, respectively. DIAGNOSES: GS was diagnosed based on the clinical symptoms, laboratory test results, and genetic analysis. GH stimulation tests were performed when the magnesium level returned to normal under magnesium oxide (MgO) therapy. INTERVENTIONS: Initially, all patients received oral replacement of MgO and potassium chloride, and 2 of them received simultaneous spironolactone therapy. Recombinant human growth hormone (rhGH) therapy was initiated after they were diagnosed with GHD. OUTCOMES: All 3 patients exhibited satisfactory growth velocity and normal serum magnesium level, although the potassium level was still slightly lower than normal. LESSONS: We suggest that all GS patients should undergo genetic evaluation, especially regarding SLC12A3 gene mutation. GHD should be considered if these patients have short stature. rhGH therapy is useful for stimulating the patients' growth, and it may increase the serum magnesium level.


Assuntos
Síndrome de Gitelman/complicações , Hormônio do Crescimento/deficiência , Criança , Pré-Escolar , Feminino , Síndrome de Gitelman/genética , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Óxido de Magnésio/uso terapêutico , Masculino , Cloreto de Potássio/uso terapêutico , Membro 3 da Família 12 de Carreador de Soluto/genética , Espironolactona/uso terapêutico
13.
Theranostics ; 9(22): 6618-6630, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588239

RESUMO

Intelligent polymeric micelles with fluorescence imaging feature have been emerged as promising tools for theranostics. However, conventional fluorescent dyes are limited by short wavelength excitation, interference of tissue autofluorescence, limited imaging depth and quenched emission in aggregation state. Methods: We synthesized a novel mPEG-SS-Poly (AEMA-co-TBIS) (mPEATss) copolymer to develop multifunctional polymeric micelles with great AIE feature for cancer therapy and AIE active two-photon bioimaging. The stimuli-responsive behavior and AIE active two-photon cell and tissue imaging as well as in vitro and in vivo antitumor ability of DOX-loaded mPEATss were studied. Results: mPEATss micelles showed excellent AIE active two-photon cell imaging ability and deep tissue imaging ability. Antitumor drug DOX could be encapsulated to form a drug-loaded micellar system with a small diameter of 65 nm. The disassembly and charge-conversion of mPEATss micelles could be triggered by acidic environment, resulting in accelerated drug release and great antitumor efficacy. In vivo, ex vivo imaging and in vivo pharmacokinetic study demonstrated that mPEATss micelles could efficiently accumulate in tumor sites, which ensured ideal anticancer effect. Conclusions: This pH and redox dual responsive and AIE active two-photon imaging polymeric micelles would be a promising candidate for theranostics.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31651138

RESUMO

As a promising biodegradable metallic material, magnesium (Mg) and its alloys have attracted special attention in the recent decade. However, challenges still remain due to its high corrosion rate and insufficient biocompatibility after implantation. In this work, we prepare a simple and versatile green tea phenol-metal induced multilayer conversion coating (Mg2+ incorporated epigallocatechin gallate (EGCG) coating) on magnesium alloys' (AZ31) substrate by layer-by-layer (LBL) method. The surface morphology results revealed that, with the incorporation of Mg2+, the as-formed EGCG/Mg coating was rich in phenol-Mg complex and presented more homogeneous and dense morphology, with far less cracks than the pure EGCG coating. The in vitro degradation rate and corrosion resistance were studied by electrochemical corrosion tests and monitoring of the changed pH value and hydrogen evolution, respectively, which revealed that the corrosion rate was effectively decreased compared to that of bare AZ31 after it was protected by EGCG/Mg coating. In vitro and ex vivo thrombogenicity test demonstrated the EGCG/Mg coatings presented an impressive improvement in decreasing the adhesion and activation of platelets and erythrocytes, in activated partial thromboplastin time (APTT), and in antithrombogenicity compared to those of bare AZ31. Owing to the mild degradation rate, in combination with the biological function of EGCG, enhanced endothelial cells' (ECs') adhesion and proliferation, suppressed smooth muscle cells' (SMCs') adhesion/proliferation, and inhibited cytokine release were observed on EGCG/Mg coated AZ31 alloy. Besides, the in vivo subcutaneous embedding experiment suggested that the EGCG/Mg coating performed more mild tissue response due to the improved corrosion resistance to the surrounding microenvironment. Moreover, for in vivo abdominal aorta assay, the EGCG/Mg coated AZ31 wire presented better corrosion resistance and enhanced re-endothelialization compared to bare AZ31 wire. These results suggested the potential of using green tea polyphenol induced Mg2+-rich multilayer conversion coating for enhanced corrosion protection and desired biocompatibility of biodegradable cardiovascular implants.

15.
Drug Metab Dispos ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31658948

RESUMO

Rat CYP2D1 has been considered as an ortholog of human CYP2D6. To assess the role of CYP2D1 in physiological processes and drug metabolism, a CYP2D1-null rat model was generated with a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 method. Seven base-pairs were deleted from the exon 4 of CYP2D1 of Sprague-Dawley wild-type (WT) rats. The CYP2D1-null rats were viable and showed no abnormalities in general appearance and behaviors. Metabolism of venlafaxine (VLF) was further studied in CYP2D1-null rats. Vmax and CLint of the liver microsomes in vitro from CYP2D1-null rats were decreased (~46% and ~57% in males, ~47% and ~58% in females), while Km was increased (~24% in males, ~25% in females) compared to those of WTs. In the pharmacokinetic studies, compared to the WTs, VLF in the CYP2D1-null rats had significantly lower Cl/F and Vd/F (~36% and ~48% in males, ~23% and ~25% in females), significantly increased AUC0-t, AUC0-∞, and Cmax (~64%, ~59% and ~26% in males, ~43%, ~35% and ~15% in females). In addition, O-desmethyl venlafaxine (the main active metabolite of venlafaxine) formation was reduced as well in the CYP2D1-null rats compared to that in WTs. Rat depression models were developed by feeding separately and chronic mild stimulations with CYP2D1-null and WT rats. VLF showed a better efficacy in the WT depression rats compared to that in the CYP2D1-null ones. In conclusion, a CYP2D1-null rat model was successfully generated, and CYP2D1 was found to play an important role in the metabolism and efficacy of venlafaxine. SIGNIFICANCE STATEMENT: A novel CYP2D1-null rat model was generated using CRISPR/Cas9 technology, and it was a valuable tool to study the in vivo function of human CYP2D6. Moreover, our data demonstrated that the reduced ODV formation was associated with a lower VLF efficacy in rats, suggesting a potential application of monitoring plasm ODV level in the clinical optimization of VLF for the treatment of depression.

16.
Esophagus ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606768

RESUMO

BACKGROUND: Esophageal motility disorders which include achalasia, esophagogastric junction outflow obstruction (EGJ outflow obstruction), jackhammer esophagus (JE), distal esophageal spasm (DES), etc. are rare disease of unknown causes. The diagnosis is based on endoscopy, barium meal, and high-resolution manometry (HRM). With the development of endoscopy, peroral endoscopic myotomy (POEM) has emerged as a standard method for the treatment of achalasia. PURPOSE: The purpose of this article is to enable gastroenterologists to have a more comprehensive understanding of the application status, technical characteristics, clinical efficacy and future prospect of POEM in the treatment of esophageal motility disorders. METHODS: Through a large number of reading literature, combined with clinical practice, summary and analysis of the indications, procedure, efficacy, complications, and controversies of POEM in the treatment of esophageal motility disorders, as well as the current and future perspectives of POEM were studied. RESULTS: POEM is safe and effective in the treatment of esophageal motility disorders, but the GERD reflux rate is higher. CONCLUSIONS: POEM can be a new option for the treatment of esophageal movement disorders, but large sample, multi-center, long-term study reports are needed, and it promotes the development of NOTES technology.

17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(4): 410-413, 2019 Jul 29.
Artigo em Chinês | MEDLINE | ID: mdl-31612677

RESUMO

OBJECTIVE: To analyze the endemic sitaution of schistosomiasis based on geographic information system (GIS) in Wuhan City in 2017, so as to provide the reference for further schistosomiasis control activities. METHODS: According to the data of the annual report on the prevention and control of schistosomiasis in Wuhan City in 2017, the spatial database regarding the endemic situation of schistosomiasis was established and analyzed by ArcMap 10.2. RESULTS: The 593 schistosomiasis-endemic villages in Wuhan City were mainly located in the Yangtze River and its major tributaries. Kernel density analysis showed that the endemic villages of three regions with the highest density was located in the west of Caidian District (Zhuru Street), the east of Hannan District (Shamao Street) and the southwest corner of Xinzhou District (Yangluo Street). The sero-positive population was densely distributed in the West of Caidian District (Zhuru Street), which accounted for 34.23% of all seruo-positives in the city. There were 492 farming cattle fenced in Donggan Village in Hongbei Street of Caidian District. A higher density of the area with Oncomelania hupensis snails was located in the southwest region of Caidian District (Xiaosi Street), accounting for 31.22% of the total area with snails. In 2017, the re-emerging area with snails was 36.60 hm2. The high kernel density region with snails was located in Zhuru Street of Caidian District. The region with high density of living snails was located in the central region of Hannan District (Hongbei Production Brigade), the average density of living snails was 0.36 snails/0.1 m2. CONCLUSIONS: The endemic situation of schistosomiasis is at a low level in Wuhan City, and the spatial distribution is not uniform. In some local areas, the historical endemic situation of schistosomiasis is serious and the high risk factors are more concentrated. It is necessary to strengthen the surveillance of schistosomiasis.


Assuntos
Sistemas de Informação Geográfica , Esquistossomose , Animais , Anticorpos Anti-Helmínticos/sangue , China/epidemiologia , Doenças Endêmicas/estatística & dados numéricos , Humanos , Densidade Demográfica , Vigilância da População , Fatores de Risco , Esquistossomose/sangue , Esquistossomose/epidemiologia , Caramujos
18.
J Phys Chem A ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31633930

RESUMO

Recent guided ion beam experiments have revealed interesting reaction dynamics of the HBr+ + CO2 → HOCO+ + Br· reaction under different conditions. The hypothesis is that the predominant reaction mechanism depends on the collision energy between two reactants, angular momentum of HBr+, and the spin-orbit coupling state of the system. The potential energy surface of the HBr+ + CO2 → HOCO+ + Br· reaction is studied in this research to lay the groundwork for an ab initio molecular dynamics simulation. First, a benchmark potential energy surface of this reaction was identified using coupled-cluster theory extrapolated to the complete basis set limit. A transition state connecting the previously reported intermediates was found, making the potential energy surface of the HBr+ + CO2 → HOCO+ + Br· reaction double welled. Second, various single reference ab initio methods were tested by comparing to the benchmark potential energy surface to search for the most suitable ab initio method for the dynamics simulation. Two combinations of double-zeta basis sets (with effective core potentials) with MP2 and density functional theory have been identified to accurately represent the potential energy surface of this reaction.

20.
Indian Pediatr ; 56(9): 789-791, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31638013

RESUMO

BACKGROUND: Prader-Willi syndrome (PWS) is a complex neurobehavioral disorder caused by failure of expression of paternally inherited genes in the PWS region of chromosome 15. CASE CHARACTERISTICS: Two siblings who both met the inclusion criteria for clinical diagnosis of PWS during neonatal period. OUTCOME: Molecular genetic analysis demonstrated a 417-kb microdeletion within the 15q11.2 region inherited from siblings' paternal grandmother, involving key genes of PWS, except for UBE3A, which may explain why their father and paternal grandmother had a normal phenotype. CONCLUSION: The findings may be helpful for better understanding of the underlying mechanism of this rare imprinting defect.

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