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1.
Int J Biol Macromol ; 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32433917

RESUMO

Skin damaged during sea battles is vulnerable to seawater immersion and bacterial infection. Scaffolds with effective biological function are highly desired for treatment of naval combat wound injuries. Herein, we prepared composite scaffolds of CS/GEL/GMs-CIP. The chitosan (CS) and gelatin (GEL) were cross-linked by genipin as matrix, and then gelatin microspheres loading ciprofloxacin hydrochloride (GMs-CIP) were add. From in vitro characterization results, CS/GEL/GMs-CIP had high water absorption ability, proper porosity, satisfactory fracture resistance, and flexibility. Furthermore, CS/GEL/GMs-CIP composite scaffold had excellent biocompatibility. Antibacterial experiments confirmed that CS/GEL/GMs-CIP had a significant inhibitory effect on E. coli, S. aureus and P. aeruginosa. The in vivo wound healing was evaluated using animal wound infection model of seawater immersion, and it was observed that the prepared composite scaffolds accelerated wound healing, reepithelialization, collagen deposition. Further analysis of wound tissue indicated that the expression of anti-inflammatory factor (TGF-ß1) was up-regulated, but the serum endotoxin levels and expression of pro-inflammatory factor (TNF-a, IL-6, and IL-1ß) were down-regulated. In summary, we believe that CS/GEL/GMs-CIP composite scaffold may serve as a promising multifunctional dressing for healing with open trauma wound infections and wound with seawater immersion.

2.
Int J Biol Macromol ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32428588

RESUMO

Cardiovascular diseases, such as hypertension and cardiac failure, have become the most major and global cause for threatening human health in recent years. Uncaria rhynchophylla as a traditional Chinese medicine is widely used to treat hypertension for a long history, whereas its medicinal effective components and potential action mechanism are uncertain. Therefore, twenty-four alkaloids (1-24) isolated from U. rhynchophylla were assayed for their relaxant effects against phenylephrine (Phe)-induced contraction of rat mesenteric arteries. Among them, we surprisingly found that uncarialin A (21) exhibited most potent relaxation effect against Phe-induced contraction (IC50 = 0.18 µM) in the manner of independent on endothelium-derived vasorelaxing factors and endothelium. All the experiments including measurement of Ca2+ in vascular smooth muscle cells (VSMCs) by fluorescence microscopy, whole-cell path clamp, molecular docking, and molecular dynamics, demonstrated that uncarialin A (21) could significantly inhibit L-type calcium channel subunit alpha-1C (Cav1.2) via the hydrogen bond interaction with amino acid residue Met1186, allowing the inhibition of Ca2+ inward current. Our results suggested that uncarialin A (21) could be served as a potential L-type Cav1.2 blocker in the effective treatment of cardiovascular diseases.

3.
Virus Res ; 285: 198019, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32417180

RESUMO

Rhabdoviruses cause devastating diseases in aquaculture, resulting in enormous economic losses. Our previous studies indicated that imidazole arctigenin derivatives possessed antiviral activities against aquatic rhabdoviruses. Based on the data of structure-activity relationship, a new imidazole arctigenin derivative, 4-(8-(2-bromoimidazole)octyloxy)-arctigenin (BOA), was designed and synthesized. And its antiviral activities against aquatic rhabdoviruses (SVCV, IHNV and MSRV) were evaluated in vitro. By comparing inhibitory concentration at half-maximal activity (IC 50), we found that BOA (IC50 = 1.11 µM) possessed a higher anti-IHNV activity than the antiviral imidazole arctigenin derivatives which were found in our previous study. Besides, BOA could cause profound inhibition of SVCV and MSRV replication. By the reduction assays on cytopathic effect, BOA exhibited a protective effect on two host cell lines. As a typical rhabdovirus, SVCV was chosen as a model to illuminate the anti-rhabdovirus mechanism of BOA. BOA was discovered to not impact directly on viral particles or interfere with SVCV adsorption. And it worked within the 2-6 h of the early phase of virus replication. In addition, after repression of cell cycle S phase and recovery of caspase-3/8/9 activities activated by SVCV, BOA inhibited SVCV-induced apoptosis and then reduced the release of viral particles at the late stage of virus replication. Altogether, BOA was expected to be a highly efficient antiviral agent against multiple rhabdoviruses in the field of aquaculture.

4.
Int J Biol Macromol ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32360461

RESUMO

The inhibition of soluble epoxide hydrolase (sEH) is regarded as a promising therapeutic approach to treat inflammation and its related disorders. In present work, we investigated inhibitory effects of forty-nine kinds of traditional Chinese medicines against sEH. Inula helenium showed significant inhibitory effect against sEH, and the extract of I. helenium were isolated to obtain eight compounds, including 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3), 8-hydroxy-9-isobutyryloxy-10(2)-methylbutyrylthymol (4), dehydrocostus lactone (5), alantolactone (6), costunolide (7), and isoalantolactone (8). Among them, 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) showed significantly inhibitory activities on sEH with half maximal inhibitory concentration (IC50) from 5.88 ±â€¯0.97 µM to 11.63 ±â€¯0.58 µM. The inhibition kinetics suggested that 4H-tomentosin (1) and xanthalongin (2) were mixed-competitive type inhibitors with inhibition constant (Ki) values of 7.02 and 6.57 µM, respectively, and linoleic acid (3) was a competitive type inhibitor with a Ki values of 3.52 µM. The potential interactions of 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) with sEH were analyzed by molecular docking, which indicated that these bioactive compounds had interactions with key amino acid residues Tyr343, Ile363, Tyr383, and His524.

5.
Braz J Infect Dis ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32389618

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and has spread rapidly worldwide. We present a mild SARS-CoV-2 infection in a baby with non-productive cough and normal chest computed tomography, in whom only anal swabs tested positive by real-time PCR testing for SARS-CoV-2. She was given atomization inhalation therapy with recombinant human interferon alfa-1b for 10 days. Her anal swabs remained positive for eight days, whereas her throat swabs were persistently negative by real-time PCR testing. Mild and asymptomatic cases, especially in children, might present with PCR negative pharyngeal/nasal swabs and PCR positive anal swabs. Those patients are potential sources of infection via fecal-oral transmission for COVID-19.

6.
FASEB J ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369233

RESUMO

Mutations in CHCHD10, a gene coding for a mitochondrial protein, are implicated in ALS-FTD spectrum disorders, which are pathologically characterized by transactive response DNA binding protein 43 kDa (TDP-43) accumulation. While both TDP-43 and CHCHD10 mutations drive mitochondrial pathogenesis, mechanisms underlying such phenotypes are unclear. Moreover, despite the disruption of the mitochondrial mitofilin protein complex at cristae junctions in patient fibroblasts bearing the CHCHD10S59L mutation, the role of CHCHD10 variants in mitofilin-associated protein complexes in brain has not been examined. Here, we utilized novel CHCHD10 transgenic mouse variants (WT, R15L, & S59L), TDP-43 transgenic mice, FTLD-TDP patient brains, and transfected cells to assess the interplay between CHCHD10 and TDP-43 on mitochondrial phenotypes. We show that CHCHD10 mutations disrupt mitochondrial OPA1-mitofilin complexes in brain, associated with impaired mitochondrial fusion and respiration. Likewise, CHCHD10 levels and OPA1-mitofilin complexes are significantly reduced in brains of FTLD-TDP patients and TDP-43 transgenic mice. In cultured cells, CHCHD10 knockdown results in OPA1-mitofilin complex disassembly, while TDP-43 overexpression also reduces CHCHD10, promotes OPA1-mitofilin complex disassembly via CHCHD10, and impairs mitochondrial fusion and respiration, phenotypes that are rescued by wild type (WT) CHCHD10. These results indicate that disruption of CHCHD10-regulated OPA1-mitofilin complex contributes to mitochondrial abnormalities in FTLD-TDP and suggest that CHCHD10 restoration could ameliorate mitochondrial dysfunction in FTLD-TDP.

7.
Phys Med Biol ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32330922

RESUMO

PURPOSE: Registration and fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) of prostate can provide guidance for prostate brachytherapy. However, accurate registration remains a challenging task due to the lack of ground-truth regarding voxel-level spatial correspondence, limited field of view, low contrast-to-noise ratio in TRUS. In this study, we proposed a weakly supervised deep learning approach to address these issues. METHODS: We employed deep learning techniques to combine image segmentation, affine and non-rigid registration to perform a deformable MRI-TRUS registration. First, we trained two separate fully convolutional neural networks to perform MRI and TRUS prostate segmentation. Then, a convolutional neural network was used to rigidly register MRI-TRUS images via affine registration. Third, a UNET-like network was applied for non-rigid registration. For both affine and non-rigid registration. Due to the unavailability of ground truth correspondences and the lack of accurate intensity-based image similarity measures, we propose to use prostate label-derived volume overlaps and surface agreements as an optimization objective function for weakly supervised network training. We proposed a hybrid loss function that integrated Dice and surface-based loss, and a bending energy regularization for the non-rigid registration. RESULTS: 36 sets of patient data were used to test our registration method. Image registration results showed that the deformed MR image aligned well with the TRUS image, as judged by corresponding cysts and calcifications in prostate. Our method produced a mean target registration error (TRE) of 2.53 ±1.39 mm and a mean Dice of 0.91±0.02. The mean surface distance (MSD) and Hausdorff distance (HD) between the registered MR prostate shape and TRUS prostate shape were 0.88 mm and 4.41 mm, respectively. CONCLUSION: This work presents a deep learning-based, weakly supervised network for accurate MRI-TURS image registration. Our proposed method has achieved promising registration performance in terms of Dice, TRE, MSD and HD.

8.
J Parkinsons Dis ; 10(2): 591-604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32250317

RESUMO

BACKGROUND: In postmortem analysis of late stage Parkinson's disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor. OBJECTIVE: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI. METHODS: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty). RESULTS: We found that smaller SN correlated with longer disease duration (r = -0.49, p = 0.004), more severe MDS-UPDRS motor score (r = -0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r = -0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume. CONCLUSIONS: In mild-to-moderate PD, SN volume relates to motor manifestations in a motor domain-specific and laterality-dependent manner. Non-invasive in vivo 7.0 Tesla QSM may serve as a biomarker in longitudinal studies of SN atrophy and in studies of people at risk for developing PD.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(4): 346-349, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32312373

RESUMO

OBJECTIVE: To study the short-term effect of two different re-induction regimens in the treatment of acute lymphoblastic leukemia (ALL) children with bone marrow recurrence. METHODS: A retrospective analysis was performed for 57 ALL children with bone marrow recurrence. According to their treatment regimen, they were divided into two groups: VMDP (vincristine + mitoxantrone + dexamethasone + PEG-asparaginase; n=42) and VIDP (vincristine + idarubicin + dexamethasone + PEG-asparaginase; n=15). The two groups were compared in terms of complete response rate and incidence rate of adverse reactions. RESULTS: There was no significant difference in complete response rate between the VMDP and VIDP groups (74% vs 73%, P>0.05). All children experienced grade ≥3 hematological adverse events. The VMDP group had a significantly lower chemotherapy-related mortality rate than the VIDP group (P<0.05). There was no significant difference in the incidence rate of infection between the two groups (P>0.05). CONCLUSIONS: For ALL children with bone marrow recurrence, both re-induction regimens can achieve a relatively high complete response rate, and VMDP regimen has a lower chemotherapy-related mortality rate and can thus be used as an option for re-induction in ALL children with bone marrow recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea , Leucemia-Linfoma Linfoblástico de Células Precursoras , Asparaginase , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Vincristina
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(4): 350-354, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32312374

RESUMO

OBJECTIVE: To study the clinical features of central nervous system infiltration-positive (CNSI+) children with acute lymphoblastic leukemia (ALL) based on flow cytometry, as well as the association of such clinical features with prognosis. METHODS: A retrospective analysis was performed for the clinical data of 66 CNSI+ children with ALL treated from April 2008 to June 2013. Clinical features, laboratory examination results and prognosis were compared between the children in different chemotherapy stages (induction stage and consolidation/maintenance stage). RESULTS: Among the 66 CNSI+ children, 50 were in the induction stage and 16 in the consolidation/maintenance stage. Compared with the CNSI+ children in the induction stage, the CNSI+ children in the consolidation/maintenance stage had a significantly higher proportion of children with the genes associated with good prognosis based on the results of molecular biology (P<0.05), as well as a significantly higher recurrence rate (P<0.05). Recurrence was observed in 21 CNSI+ ALL children, among whom 10 were in the induction stage and 11 were in the consolidation/maintenance stage. Compared with the children experiencing recurrence in the induction stage, the children experiencing recurrence in the consolidation/maintenance stage had a significantly higher proportion of children with recurrence of the central nervous system and bone marrow (P<0.05), as well as significantly higher proportion of biochemical positive rate of cerebrospinal fluid (P<0.05). The children in the induction stage had a significantly higher recurrence-free survival rate than those in the consolidation/maintenance stage (P<0.001), while there was no significant difference in overall survival rate between the two groups (P>0.05). CONCLUSIONS: In children with ALL, CNSI+ has a marked effect on recurrence-free survival rate in different chemotherapy stages, but has no obvious effect on overall survival rate. CNSI+ patients in the consolidation/maintenance stage have a higher recurrence.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Intervalo Livre de Doença , Humanos , Prognóstico , Recidiva , Estudos Retrospectivos
11.
J Agric Food Chem ; 68(19): 5384-5390, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32275147

RESUMO

Aspergillus niger mycelial waste is a good raw material for production of N-acetyl-d-glucosamine (GlcNAc). In this study, AnChiB, an A. niger chitinase which is upregulated during autolysis, was found to degrade A. niger mycelial waste with high efficiency. It could produce 1.45 mM (GlcNAc)2 in 8 h from raw mycelial waste, outperforming other chitinases, including bacterial SmChiA, human HsCht, and insect OfChtI and OfChi-h. The crystal structure of AnChiB was determined, and residues Trp106 and Trp118 were found to be important for the activity of AnChiB toward mycelial waste; mutation of either Trp106 or Trp118 into phenylalanine or alanine resulted in dramatically decreased activity. A recombinant strain of Bacillus subtilis was constructed to extracellularly produce AnChiB, and the culture supernatant was used to treat mycelial waste. This eco-friendly strategy could produce 3.7 mM of GlcNAc from 10 g of mycelial waste in 94 h with a yield of 71.3%.

12.
Med Phys ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323330

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study is to develop a deep learning-based approach to simultaneously segment five pelvic organs including prostate, bladder, rectum, left and right femoral heads on cone-beam CT (CBCT), as required elements for prostate adaptive radiotherapy planning. MATERIALS AND METHODS: We propose to utilize both CBCT and CBCT-based synthetic MRI (sMRI) for the segmentation of soft tissue and bony structures, as they provide complementary information for pelvic organ segmentation. CBCT images have superior bony structure contrast and sMRIs have superior soft tissue contrast. Prior to segmentation, sMRI was generated using a cycle-consistent adversarial networks (CycleGAN), which was trained using paired CBCT-MR images. To combine the advantages of both CBCT and sMRI, we developed a cross-modality attention pyramid network with late feature fusion. Our method processes CBCT and sMRI inputs separately to extract CBCT-specific and sMRI-specific features prior to combining them in a late-fusion network for final segmentation. The network was trained and tested using 100 patients' datasets, with each dataset including the CBCT and manual physician contours. For comparison, we trained another two networks with different network inputs and architectures. The segmentation results were compared to manual contours for evaluations. RESULTS: For the proposed method, dice similarity coefficients and mean surface distances between the segmentation results and the ground truth were 0.96 ± 0.03, 0.65 ± 0.67 mm; 0.91 ± 0.08, 0.93 ± 0.96 mm; 0.93 ± 0.04, 0.72 ± 0.61 mm; 0.95 ± 0.05, 1.05 ± 1.40 mm; and 0.95 ± 0.05, 1.08 ± 1.48 mm for bladder, prostate, rectum, left and right femoral heads, respectively. As compared to the other two competing methods, our method has shown superior performance in terms of the segmentation accuracy. CONCLUSION: We developed a deep learning-based segmentation method to rapidly and accurately segment five pelvic organs simultaneously from daily CBCTs. The proposed method could be used in the clinic to support rapid target and organs-at-risk contouring for prostate adaptive radiation therapy.

13.
Nanoscale ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236196

RESUMO

Structural defects in crystals are generally believed to disrupt the symmetry of the pristine lattice, but sometimes, they can also serve as the constituent elements of new structures if they are arranged in a well-ordered pattern. Herein, choosing 2D transition metal dichalcogenides (TMDCs) as a model system, we successfully fabricated a novel group of 2D materials-M2X3 (M = Mo, W, X = S, Se) via the periodic assembly of chalcogen vacancy lines in their corresponding MX2 monolayers (such as MoS2). Our ab initio calculations further revealed that these monolayer M2X3 materials electronically exhibit quasi-direct narrow band-gap semiconducting characteristics, e.g., Eg = 0.89 eV for Mo2S3, and show ultra-high phonon-limited room-temperature carrier mobility up to ∼27 000 cm2 V-1 s-1 for electrons in Mo2S3. The emergence of these novel M2X3 materials expands the existing 2D family and provides new platforms for both fundamental research and practical applications, and the approach via the periodic assembly of ordered defects should also be applicable to other 2D materials.

14.
Zhongguo Zhong Yao Za Zhi ; 45(2): 367-373, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237320

RESUMO

To identify and verify the active ingredients from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology and heart RNA-sequencing data. The monomers of A. membranaceus and their intervention target database were established by using network pharmacology. The genes associated to cardiac remodeling were then screened by analyzing cardiac RNA-sequencing data. An overlap between genes related to cardiac remodeling and targets of ingredients form A. membranaceus was collected to obtain monomers with protective effect on hypertensive cardiac remodeling. Angiotensin Ⅱ(AngⅡ)-induced mouse cardiac remodeling model was used to validate the protective effect of active ingredients from A. membranaceus on hypertensive cardiac remodeling. Finally, a total of 81 monomers and 1 197 targets were enrolled in our database. Mouse RNA-sequencing data showed that 983 genes were significantly up-regulated and 465 genes were down-regulation in myocardial tissues of the cardiac remodeling mice as compared with blank group mice, respectively. Ninety-two genes were found via overlapping between genes related to cardiac remodeling and targets, involving 59 monomers from A. membranaceus. Further research found that vanillic acid(VA) could intervene 27 genes associated with hypertensive cardiac remodeling, ranking top 1. Meanwhile, VA could significantly inhibit AngⅡ-induced increase in ratio of heart weight to body weight and heart weight to tibial length, ANP and BNP mRNA levels in myocardial tissues, myocardial tissue damage, cardiac fibrosis level and cardiac hypertrophy level in vivo. Those results showed that network pharmacology screen-based VA has protective effect on AngⅡ-induced cardiac remodeling.

15.
Hum Vaccin Immunother ; : 1-7, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343618

RESUMO

Purpose: To estimate influenza-associated excess mortality rates (EMRs) in Chongqing from 2012 to 2018.Methods: We obtained weekly mortality data for all-cause and four underlying causes of death (circulatory and respiratory disease (CRD), pneumonia and influenza (P&I), chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IDH)), and influenza surveillance data, from 2012 to 2018. A negative-binomial regression model was used to estimate influenza-associated EMRs in two age groups (<65 years and ≥65 years).Results: It was estimated that an annual average of 10025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths. The average EMR for all-cause death associated with influenza was 33.5 (95% confidence interval (CI): 31.5-35.6) per 100 000 persons, and in separate cause-specific models we attributed 24.7 (95% CI: 23.3-26.0), 0.8 (95% CI: 0.7-0.8), 8.5 (95% CI: 8.1-9.0) and 5.0 (95% CI: 4.7-5.3) per 100 000 persons EMRs to CRD, P&I, COPD and IDH, respectively. The estimated EMR for influenza B virus was 20.6 (95% CI: 20.3-21.0), which was significantly higher than the rates of 5.3 (95% CI: 4.5-6.1) and 7.5 (95% CI: 6.7-8.3) for A(H3N2) and A(H1N1) pdm09 virus, respectively. The estimated EMR was 152.3 (95% CI: 136.1-168.4) for people aged ≥65 years, which was significantly higher than the rate for those aged <65 years (6.8, 95% CI: 6.3-7.2).Conclusions: Influenza was associated with substantial EMRs in Chongqing, especially among elderly people. Influenza B virus caused a relatively higher excess mortality impact compared with A(H1N1)pdm09 and A(H3N2). It is advisable to optimize future seasonal influenza vaccine reimbursement policy in Chongqing to curb disease burden.

16.
Sci China Life Sci ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32347474

RESUMO

Phloretin is an important skin-lightening and depigmenting agent from the peel of apples. Although de novo production of phloretin has been realized in microbes using the natural pathway from plants, the efficiency of phloretin production is still not enough for industrial application. Here, we established an artificial pathway in the yeast to produce phloretin via assembling two genes of p-coumaroyl-CoA ligase (4CL) and chalcone synthase (CHS). CHS is a key enzyme which conventionally condenses a CoA-tethered starter with three molecules of malonyl-CoA to form the backbone of flavonoids. However, there was 33% of by-product generated via CHS by condensing two molecules of malonyl-CoA during the fermentation process. Hence, we introduced a more efficient CHS and improved the supply of malonyl-CoA through two pathways; the by-product ratio was decreased from 33% to 17% and the production of phloretin was improved from 48 to 83.2 mg L-1. Finally, a fed-batch fermentation process was optimized and the production of phloretin reached 619.5 mg L-1, which was 14-fold higher than that of the previous studies. Our work established a platform for the biosynthesis of phloretin from the low-cost raw material 3-(4-hydroxyphenyl) propanoic acid and also illustrated the potential for industrial scale bio-manufacturing of phloretin.

17.
Biosci Rep ; 40(4)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32323724

RESUMO

The association between lung and intestine has already been reported, but the differences in community structures or functions between lung and intestine bacteria yet need to explore. To explore the differences in community structures or functions, the lung tissues and fecal contents in rats were collected and analyzed through 16S rRNA sequencing. It was found that intestine bacteria was more abundant and diverse than lung bacteria. In intestine bacteria, Firmicutes and Bacteroides were identified as major phyla while Lactobacillus was among the most abundant genus. However, in lung the major identified phylum was Proteobacteria and genus Pseudomonas was most prominent genus. On the other hand, in contrast the lung bacteria was more concentrated in cytoskeleton and function in energy production and conversion. While, intestine bacteria were enriched in RNA processing, modification chromatin structure, dynamics and amino acid metabolism. The study provides the basis for understanding the relationships between lung and intestine bacteria.

18.
Transl Stroke Res ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323149

RESUMO

Intracerebral hemorrhage (ICH) is a catastrophic stroke with high mortality, and the mechanism underlying ICH is largely unknown. Previous studies have shown that high serum uric acid (SUA) levels are an independent risk factor for hypertension, cardiovascular disease (CVD), and ischemic stroke. However, our metabolomics data showed that SUA levels were lower in recurrent intracerebral hemorrhage (R-ICH) patients than in ICH patients, indicating that lower SUA might contribute to ICH. In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II)-induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is the first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrovascular rupture during the ICH process.

19.
Phys Med Biol ; 65(9): 095012, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32182595

RESUMO

Epicardial adipose tissue (EAT) is a visceral fat deposit, that's known for its association with factors, such as obesity, diabetes mellitus, age, and hypertension. Segmentation of the EAT in a fast and reproducible way is important for the interpretation of its role as an independent risk marker intricate. However, EAT has a variable distribution, and various diseases may affect the volume of the EAT, which can increase the complexity of the already time-consuming manual segmentation work. We propose a 3D deep attention U-Net method to automatically segment the EAT from coronary computed tomography angiography (CCTA). Five-fold cross-validation and hold-out experiments were used to evaluate the proposed method through a retrospective investigation of 200 patients. The automatically segmented EAT volume was compared with physician-approved clinical contours. Quantitative metrics used were the Dice similarity coefficient (DSC), sensitivity, specificity, Jaccard index (JAC), Hausdorff distance (HD), mean surface distance (MSD), residual mean square distance (RMSD), and the center of mass distance (CMD). For cross-validation, the median DSC, sensitivity, and specificity were 92.7%, 91.1%, and 95.1%, respectively, with JAC, HD, CMD, MSD, and RMSD are 82.9% ± 8.8%, 3.77 ± 1.86 mm, 1.98 ± 1.50 mm, 0.37 ± 0.24 mm, and 0.65 ± 0.37 mm, respectively. For the hold-out test, the accuracy of the proposed method remained high. We developed a novel deep learning-based approach for the automated segmentation of the EAT on CCTA images. We demonstrated the high accuracy of the proposed learning-based segmentation method through comparison with ground truth contour of 200 clinical patient cases using 8 quantitative metrics, Pearson correlation, and Bland-Altman analysis. Our automatic EAT segmentation results show the potential of the proposed method to be used in computer-aided diagnosis of coronary artery diseases (CADs) in clinical settings.

20.
J Am Chem Soc ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32212652

RESUMO

Hydrogen-bonded organic frameworks (HOFs) show great potential in many applications, but few structure-property correlations have been explored in this field. In this work, we report that self-assembly of a rigid and planar ligand gives rise to flat hexagonal honeycomb motifs which are extended into undulated two-dimensional (2D) layers and finally generate three polycatenated HOFs with record complexity. This kind of undulation is absent in the 2D layers built from a very similar but nonplanar ligand, indicating that a slight torsion of ligand produces overwhelming structural change. This change delivers materials with unique stepwise adsorption behaviors under a certain pressure originating from the movement between mutually interwoven hexagonal networks. Meanwhile, high chemical stability, phase transformation, and preferential adsorption of aromatic compounds were observed in these HOFs. The results presented in this work would help us to understand the self-assembly behaviors of HOFs and shed light on the rational design of HOF materials for practical applications.

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