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1.
Cell Death Dis ; 11(5): 302, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358484

RESUMO

Tumor-associated neutrophils (TANs) are important inflammatory infiltrating cells in the tumor microenvironment and are closely related to the development of human tumor. However, the underlying mechanism of TANs recruiting to glioma remains unknown. Herein, we identified that LINC01116 was significantly upregulated in glioma, and positively correlated with clinical malignancy and survival prognosis. LINC01116 regulated the progression of glioma in vitro and in vivo. RNA-seq analysis demonstrated that LINC01116 knockdown affected the expression of IL-1ß, which promoted glioma proliferation and neutrophil recruitment. Furthermore, the co-culture of glioma cells and neutrophils showed that the accumulation of TANs promoted tumor proliferation via producing a host of cytokines. Mechanistically, LINC01116 activated IL-1ß expression by recruiting the transcriptional regulator DDX5 to the IL-1ß promoter. Our findings reveal that LINC01116 can promote glioma proliferation and neutrophil recruitment by regulating IL-1ß, and may be served as a novel target for glioma therapy and prognosis.

2.
J Chemother ; : 1-11, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32441568

RESUMO

The aim of this study was to evaluate the impact of inflammation on voriconazole (VRCZ) metabolism at three age groups in the allogeneic hematopoietic cell transplant recipients of the Chinese population. The study was performed with collecting more than one VRCZ trough concentration and C-reactive protein (CRP) levels. Longitudinal analysis, correlation and comparative analysis were conducted to evaluate. A total of 104 patients with 386 VRCZ trough concentration and CRP level measured on the same day were collected. For children, CRP levels significantly associated with VRCZ pharmacokinetics in age 11-18 years but not in age 2-10 years. For adults, VRCZ concentrations were increased slightly by 0.006 mg/L when every 1 mg/L increased in CRP levels. Additionally, meropenem and inflammation might work together to cause a higher VRCZ concentration. Therefore, therapeutic drug monitoring of VRCZ should be warranted at age >10 years in allogeneic hematopoietic cell transplant recipients with elevated CRP level.

3.
Int J Surg ; 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32461196

RESUMO

BACKGROUND: Recently, the effects of erector spinae plane block on postoperative pain have become increasingly controversial. This meta-analysis compared the effects of ESP block versus placebo on postoperative analgesia and side effects to determine whether the new technique is a reliable alternative for pain management. METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Database were searched for clinical studies investigating the analgesic effect of ESP block versus placebo. The primary outcomes included the visual analogue scale (VAS) at rest and during movement, as well as the postoperative morphine consumption in 24 h, and the secondary outcome was the rate of postoperative nausea and vomiting (PONV). The choice of using the fixed or random-effects model depended on whether the heterogeneity tested by I2 statistic was more than 50%. Seeking sources of heterogeneity and exploring the effect of clinical details on the final result were performed by subgroup analysis. Additionally, the test for stability of the pooled result was realized by sensitivity analysis. Finally, we evaluated the quality of the evidence for the outcomes. STATA 13.0 software was selected as the main analysis software in the meta-analysis. RESULTS: Eighteen randomized controlled trials (RCTs) comprising 1041 patients were reviewed. This meta-analysis showed that ESP block could significantly reduce patients' pain scores at 1 h, 6 h, 12 h, and 24 h after surgery at rest or during movement; 24-h postoperative morphine consumption; and the incidence of PONV. CONCLUSIONS: ESP block as a novel technique exhibited superior postoperative analgesic effects, reducing the postoperative complications in spinal, thoracic, and abdominal surgeries during the early postoperative period. However, as a new nerve block technique, numerous large-sized RCTs are needed for further research.

4.
RNA ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32371455

RESUMO

RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA 3D structure prediction. With agreement from crystallographers, the RNA structures are predicted by various groups before the publication of the crystal structures. We now report the prediction of six RNA sequences: four structures of nucleolytic ribozymes and two of riboswitches. Systematic protocols for comparing models and crystal structures are described and analyzed. In these six puzzles, we discuss a) the comparison between the automated web server and human experts; b) the prediction of coaxial stacking; c) the prediction of structural details and ligand binding; d) the development of novel prediction methods; and e) the potential improvements to be made. It is illustrated that correct coaxial stacking and tertiary contacts are key for the prediction of RNA architecture, while ligand binding modes can be only predicted with low resolution and accurate ligand binding prediction still remains out of reach. All the predicted models are available for the future development of force field parameters and the improvement of comparison and assessment tools.

5.
J Biophotonics ; : e202000011, 2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32362070

RESUMO

Limb perfusion monitoring is critical for diabetes mellitus (DM) patients as they are vulnerable to vascular complications due to prolonged hyperglycemia. However, current clinical approaches are ineffective in vascular imaging and in assessing vascular function in lower limbs. In this work, a concave ultrasound transducer array-based photoacoustic tomography (PAT) system was used to image the foot dorsal section of a subject, and a total of seven DM patients and seven healthy volunteers were enrolled in this study. Hemodynamic changes in foot vessels during vascular occlusion as well as oxygen saturation (SO2 ) in rest were analyzed for both groups. The results obtained showed that DM patients have a unique peripheral hemodynamic response to occlusion and a lower level SO2 , compared to that for healthy subjects. This suggests that PAT has the potential to detect vascular dysfunction in DM patients and to measure the effect of treatment.

6.
J Clin Lab Anal ; 34(5): e23204, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32406547

RESUMO

BACKGROUND: Hip fracture in the elderly is a health burden worldwide due to its high mortality rate. This study was conducted to determine the possible mechanisms of osteopontin (OPN) and ß-carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTX) in hip fracture in the elderly. MATERIALS AND METHODS: In the study, we recruited 108 elderly patients with hip fracture diagnosed from May 2012 to May 2015 at the Third Hospital of Xiamen and 86 healthy individuals without a history of hip fracture were taken as controls. Serum levels of OPN and ß-CTX were then determined. The T and Z values for bone mineral density (BMD) were also measured. Moreover, logistic regression analysis was performed to assess the risk and protective factors for hip fracture in the elderly. RESULTS: Serum levels of both OPN and ß-CTX were increased in elderly patients with hip fracture. OPN was positively correlated with ß-CTX. In addition, the levels of OPN and ß-CTX shared a positive association with the age, and a negative association with the BMD, in terms of T and Z values of the hip. In addition, increased BMD and outdoor sports might be protective factors for hip fracture, and an increase in levels of OPN and ß-CTX might be associated with a higher risk of hip fracture in the elderly population. DISCUSSION: Collectively, increased serum levels of OPN and ß-CTX might be correlated with a higher risk of a hip fracture and have predictive values in the occurrence of hip fracture in the elderly.

7.
Nat Commun ; 11(1): 2595, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444620

RESUMO

The anterior temporal lobes (ATL) have become a key brain region of interest in cognitive neuroscience founded upon neuropsychological investigations of semantic dementia (SD). The purposes of this investigation are to generate a single unified model that captures the known cognitive-behavioural variations in SD and map these to the patients' distribution of frontotemporal atrophy. Here we show that the degree of generalised semantic impairment is related to the patients' total, bilateral ATL atrophy. Verbal production ability is related to total ATL atrophy as well as to the balance of left > right ATL atrophy. Apathy is found to relate positively to the degree of orbitofrontal atrophy. Disinhibition is related to right ATL and orbitofrontal atrophy, and face recognition to right ATL volumes. Rather than positing mutually-exclusive sub-categories, the data-driven model repositions semantics, language, social behaviour and face recognition into a continuous frontotemporal neurocognitive space.

8.
Gene ; 752: 144790, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32439376

RESUMO

Many anatomical regions in the kidney, including proximal tubules, differ between males and females. While such differences in renal structures and functions under various physiological and pharmacological conditions have been identified, information relating to molecular mechanisms behind this gender disparity remain unknown. To understand gene expression differences in proximal tubules from human male and female kidneys, we reported on kidney cellular landscape using single-cell RNA sequencing. Differential gene expression profiles were observed in proximal tubules, between the sexes. Interestingly, the SLC22 family of anion transporters, including SLC22A6 and SLC22A8, had different expression profiles between male and female proximal tubule clusters but not sex-dependent abundance at the protein level. Moreover, in different species, we revealed a shared and species-specific differential gene expression between human and mouse kidney proximal tubules. Taken together, at single-cell resolution, this transcriptomic map represents a baseline description of gender biased genes in human kidney proximal tubules, which provide important insights for further studies of physiological differences in kidney.

9.
Food Funct ; 11(4): 3332-3350, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32226990

RESUMO

α-Glucosidase (AG) has always been an indispensable drug target for the treatment of type 2 diabetes. Herein, an integrated method consisting of enzyme kinetics, multi-spectroscopy assay and molecular simulations was used to investigate the structure-activity relationship and interaction mechanism of flavonoids and AG. As a result, a small amount of flavonoids was found to present excellent inhibitory activity on AG, such as 3, 5, 6, 8, 10, 17, 19, 21, 22 and 34. Further analysis of the structure-activity relationship illustrated that hydroxylation at the positions C3, C6, C3' and C4' of flavonoids caused an increase in the inhibitory activity of AG, whereas the methoxylation at the corresponding positions would decrease the activity. Also, it was found that the glycosylation and hydrogenation of the C2[double bond, length as m-dash]C3 double bond would distinctly reduce the inhibition potency. Therefore, various groups at different positions of flavonoids exhibited an upward and downward tendency in the activity. According to the fluorescence quenching assay, all of the test flavonoids could effectively quench the intrinsic fluorescence of AG based on either the static or mixed static-dynamic mechanism. Besides, the thermodynamic parameters of the representative flavonoid 19 revealed the spontaneous characteristic of the binding process with AG, and highlighted the critical role of the hydrophobic interaction and hydrogen bonds. Moreover, the results obtained from the synchronous fluorescence, ANS-binding fluorescence, Fourier transform infrared and circular dichroism spectra illustrated that these active flavonoids could bind to the active site of AG and induce the rearrangement and conformation change of its secondary structures, which resulted in a significant inhibitory activity. Additionally, molecular modelling visualized the preferred binding conformation of flavonoids on AG, and further confirmed the great importance of the hydrophobic interaction and hydrogen bonds in the interaction. Such findings provided new insights for understanding the proposed interaction behavior between flavonoids and AG, and were helpful to develop novel AG inhibitors relying on the flavonoid scaffold for the treatment of type 2 diabetes.

10.
Adv Mater ; : e2000906, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32342553

RESUMO

Diagnostics is the key in screening and treatment of cancer. As an emerging tool in precision medicine, metabolic analysis detects end products of pathways, and thus is more distal than proteomic/genetic analysis. However, metabolic analysis is far from ideal in clinical diagnosis due to the sample complexity and metabolite abundance in patient specimens. A further challenge is real-time and accurate tracking of treatment effect, e.g., radiotherapy. Here, Pd-Au synthetic alloys are reported for mass-spectrometry-based metabolic fingerprinting and analysis, toward medulloblastoma diagnosis and radiotherapy evaluation. A core-shell structure is designed using magnetic core particles to support Pd-Au alloys on the surface. Optimized synthetic alloys enhance the laser desorption/ionization efficacy and achieve direct detection of 100 nL of biofluids in seconds. Medulloblastoma patients are differentiated from healthy controls with average diagnostic sensitivity of 94.0%, specificity of 85.7%, and accuracy of 89.9%, by machine learning of metabolic fingerprinting. Furthermore, the radiotherapy process of patients is monitored and a preliminary panel of serum metabolite biomarkers is identified with gradual changes. This work will lead to the application-driven development of novel materials with tailored structural design and establishment of new protocols for precision medicine in near future.

11.
Sci Rep ; 10(1): 6662, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313127

RESUMO

The environment affects the composition and function of soil microbiome, which indirectly influences the quality of plants. In this study, 16S amplicon sequencing was used to reveal the differences in soil microbial community composition of Cistanche deserticola in three ecotypes (saline-alkali land, grassland and sandy land). Through the correlation analysis of microbial community abundance, phenylethanoid glycoside contents and ecological factors, the regulatory relationship between microbial community and the quality variation of C. deserticola was expounded. The metabolic function profile of soil microbiome was predicted using Tax4Fun. Data showed that the soil microbial communities of the three ecotypes were significantly different (AMOVA, P < 0.001), and the alpha diversity of grassland soil microbial community was the highest. Core microbiome analysis demonstrated that the soil microbial communities of C. deserticola were mostly have drought, salt tolerance, alkali resistance and stress resistance, such as Micrococcales and Bacillales. The biomarkers, namely, Oceanospirillales (saline-alkali land), Sphingomonadales (grassland) and Propionibacteriales (sandy land), which can distinguish three ecotype microbial communities, were excavated through LEfSe and random forest. Correlation analysis results demonstrated that 2'-acetylacteoside is positively correlated with Oceanospirillales in saline-alkali land soil. The metabolic function profiles displayed highly enriched metabolism (carbohydrate and amino acid metabolisms) and environmental information processing (membrane transport and signal transduction) pathways. Overall, the composition and function of soil microbiomes were found to be important factors to the quality variation of C. deserticola in different ecotypes. This work provided new insight into the regulatory relationship amongst the environment, soil microbial community and plant quality variation.

12.
Food Chem ; 323: 126807, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32330646

RESUMO

In this study, some flavonoids were screened as potent xanthine oxidase (XO) inhibitors in vitro. Flavonoid 9 was demonstrated to exhibit the inhibitory activity through a ping-pong mechanism. Further structure-activity relationship revealed that different structural elements had greatly influenced the inhibition effect on XO and underlined the requirement of hydroxyl groups at C5 and C4' of flavonoid type I. Moreover, some bioactive flavonoids could efficiently quench the intrinsic fluorescence of XO by either static or static-dynamic mixed mechanism. The synchronous fluorescence, ANS-binding fluorescence, Fourier transform infrared spectra and circular dichroism suggested that active flavonoids could bind to the active center of XO, prevent the entrance of substrate, and induce the rearrangement and conformation change of its secondary structures, ultimately resulting in the significant inhibition effect. Additionally, molecular docking further confirmed these conclusions and highlighted the great importance of hydrophobic interactions and hydrogen bonds for the formation of stable complex conformation.

13.
Nucleic Acids Res ; 48(9): 5094-5105, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32297938

RESUMO

Box C/D RNA protein complexes (RNPs) catalyze site-specific 2'-O-methylation of RNA with specificity determined by guide RNAs. In eukaryotic C/D RNP, the paralogous Nop58 and Nop56 proteins specifically associate with terminal C/D and internal C'/D' motifs of guide RNAs, respectively. We have reconstituted active C/D RNPs with recombinant proteins of the thermophilic yeast Chaetomium thermophilum. Nop58 and Nop56 could not distinguish between the two C/D motifs in the reconstituted enzyme, suggesting that the assembly specificity is imposed by trans-acting factors in vivo. The two C/D motifs are functionally independent and halfmer C/D RNAs can also guide site-specific methylation. Extensive pairing between C/D RNA and substrate is inhibitory to modification for both yeast and archaeal C/D RNPs. N6-methylated adenine at box D/D' interferes with the function of the coupled guide. Our data show that all C/D RNPs share the same functional organization and mechanism of action and provide insight into the assembly specificity of eukaryotic C/D RNPs.

14.
Animals (Basel) ; 10(3)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244964

RESUMO

The objective of this study was to explore the molecular mechanism for male sterility of yak hybrids based on two demethylases. Total RNA was extracted from the testes of adult yaks (n = 10) and yak hybrids (cattle-yaks, n = 10). The coding sequences (CDS) of two lysine demethylases (KDMs), KDM1A and KDM4B, were cloned by RT-PCR. The levels of KDM1A and KDM4B in yaks and cattle-yaks testes were detected using Real-time PCR and Western blotting for mRNA and protein, respectively. In addition, the histone methylation modifications of H3K36me3 and H3K27me3 were compared between testes of yaks and cattle-yaks using ELISA. The CDS of KDM1A and KDM4B were obtained from yak testes. The results showed that the CDS of KDM1A exhibited two variants: variant 1 has a CDS of 2622 bp, encoding 873 amino acids, while variant 2 has a CDS of 2562 bp, encoding 853 amino acids. The CDS of the KDM4B gene was 3351 bp in length, encoding 1116 amino acids. The mRNA and protein expression of KDM1A and KDM4B, as well as the level of H3K36me3, were dramatically decreased in the testes of cattle-yaks compared with yaks. The present results suggest that the male sterility of cattle-yaks might be associated with reduced histone methylation modifications.

15.
Sci Rep ; 10(1): 6151, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32273561

RESUMO

The establishment of the Sanjiangyuan National Park (SNP) favours implementation of strictest ecological protection on the Tibetan Plateau, thus firmly ensuring national ecological security. To understand ecological background in the SNP, spatial and temporal variations of ecosystem, and its services during the period 2000-2015 and significance identification were analysed by using the methods of remote sensing, GIS and model simulation. The results showed that: (1) Area with extremely important ecosystem services accounted for approximately 51.4% of the SNP's total area, of which extreme importance water regulation, soil conservation and sand fixation regions contributed 15.3%, 13.7% and 22.4%, respectively. (2) The SNP had formed a spatial pattern of ecosystem services with water regulation as core in the eastern part, soil conservation as core in the central part and sand fixation as core in the western part. (3) For the period 2000-2015, water regulation service generally improved in the SNP. Soil conservation service also improved overall; and sand fixation service exhibited a decreasing trend due to reduction in wind speed and vegetation coverage. (4) Climate warming and humidification, combined with the implementation of ecological protection project in the SNP were the primary reasons for ecosystem services improvement. However, grassland degradation had not yet been fundamentally suppressed, and vegetation coverage was still declining in regional areas. For strict protection and sustainable use of the SNP and its natural resources, overall planning and scientific layout should be paid more attention, and classification and subarea protection should be implemented based on natural ecosystem laws.

16.
RNA ; 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295864

RESUMO

The nadA motif is the first known NAD+-dependent riboswitch, comprising two similar tandem bulged stem-loop structures. We have determined the structure of the 5' domain 1 of the riboswitch. It has three coaxial helical segments, separated by an ACANCCCC bulge and by an internal loop, with a tertiary contact between them that includes two C:G base pairs. We have determined the structure with a number of ligands related to NADH, but in each case only the ADP moiety is observed. The adenosine adopts an anti conformation, and forms multiple hydrogen bonds across the width of the sugar edge of the penultimate C:G base pair of the helix preceding the bulge, and the observed contacts have been confirmed by mutagenesis and calorimetry. Two divalent metal ions play a key structural role at the narrow neck of the bulge. One makes direct bonding contacts to the di-phosphate moiety, locking it into position. Thus the nucleobase, ribose and phosphate groups of the ADP moiety are all specifically recognised by the RNA. The NAD+ riboswitch is modular. Domain 1 is an ADP binding domain that may be ancient, and could potentially be used in combination with other ligand binding motifs such as CoA.

17.
J Matern Fetal Neonatal Med ; : 1-6, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32283961

RESUMO

Objective: We aim to establish a formula calculating the fetal cavum septi pellucidi (CSP) width Z-scores and compare CSP width between the normal fetus and 18-trisomy fetus.Methods: In this retrospective study, 608 normal fetuses and 71 fetuses with the 18-trisomy syndrome were included. Z-scores were calculated after the acquisition of CSP images. Normal CSP width Z-scores formulae were constructed based on gestational age (GA) by performing a standard regression analysis followed by weighted regression of absolute residual values. Subsequently, the Mann-Whitney U test was used to compare the CSP width Z-scores between normal and 18-trisomy groups.Results: Formulae calculating CSP width Z-scores were constructed. Normal fetal CSP width was significantly correlated with GA (R2 = 0.50, p < .01). In 18-trisomy group, 69% (34/49) fetuses displayed enlarged fetal CSP width and CSP width Z-scores (p < .01).Conclusions: The CSP width Z-scores formulae established in the current study can provide a quantitative basis for the prenatal diagnosis of 18-trisomy syndrome. Enlarged CSP width Z-score may serve as a novel prenatal diagnostic marker for the 18-trisomy syndrome.

19.
Nat Commun ; 11(1): 1654, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245966

RESUMO

Cardiovascular diseases lead to 31.5% of deaths globally, and particularly myocardial infarction (MI) results in 7.4 million deaths per year. Diagnosis of MI and monitoring for prognostic use are critical for clinical management and biomedical research, which require advanced tools with accuracy and speed. Herein, we developed a plasmonic gold nano-island (pGold) chip assay for diagnosis and monitoring of MI. On-chip microarray analysis of serum biomarkers (e.g., cardiac troponin I) afforded up to 130-fold enhancement of near-infrared fluorescence for ultra-sensitive and quantitative detection within controlled periods, using 10 µL of serum only. The pGold chip assay achieved MI diagnostic sensitivity of 100% and specificity of 95.54%, superior to the standard chemiluminescence immunoassay in cardiovascular clinics. Further, we monitored biomarker concentrations regarding percutaneous coronary intervention for prognostic purpose. Our work demonstrated a designed approach using plasmonic materials for enhanced diagnosis and monitoring for prognostic use towards point-of-care testing.

20.
World Neurosurg ; 139: 322-329, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32311548

RESUMO

BACKGROUND: Solitary plasmacytoma of bone (SPB) is a rare malignancy of localized osseous lesion consisting of neoplastic monoclonal plasma cells. Recommended treatment of SPB includes a combination of surgery and radiation therapy. We present a rare case of SPB lesion in the atlas requiring surgical resection, followed by restoration of atlas stability with a custom 3-dimensional-printed (3DP) patient-specific implant (PSI). CASE DESCRIPTION: A 57-year-old man presented with severe neck pain. Assessment by radiographs, computed tomography, and magnetic resonance imaging was found to harbor a single osteolytic lesion at the C1 (atlas) vertebra. Diagnostic tumor screening returned negative results. Transoral biopsy suggested solitary plasmacytoma. Spinal instability was apparent-hence the decision for surgical intervention via the retropharyngeal external approach to resect the lesion. Atlas reconstruction and stabilization were achieved using a custom 3DP titanium PSI. Subsequent pathologic findings confirmed plasma cell infiltration of the atlas. Histologic evaluations and cytogenetic risk analysis indicated a non-high-risk SPB. The patient was given localized radiation therapy at 57 Gy in 27 fractions. Her neurologic complaints were subsequently relieved, and mobility was restored 7 days postoperatively. CONCLUSIONS: No consensus on the appropriate surgical approaches and perioperative strategies for spinal SPB exists. Surgical intervention is recommended when vertebral instability is evident, followed by radiation therapy to minimize local recurrence and/or progression to multiple myeloma. The use of 3D modeling for preoperative planning improves intraoperative accuracy and avoids iatrogenic injuries to vital anatomic structures. Customized 3DP-PSI to restore atlas stability is an effective option for the treatment of spinal SPBs.

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