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1.
Food Chem ; 305: 125476, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525589

RESUMO

Octenylsuccinate quinoa starch (OSQS) granule that stabilized Pickering emulsion gel with different gel networks by modulating the oil volume fraction (Φ) was developed as a carrier for lutein. Pickering emulsion gels stabilized by OSQS were achieved at Φ values ranging from 30% to 60%. Increasing Φ progressively increased the droplet size, storage modulus, and apparent viscosity, resulting in the formation of gel-like structure. Confocal laser scanning microscopy showed that OSQS formed a densely packed layer at the oil/water interface, the degree of aggregation between droplets increased, and the gel network enhanced through droplet flocculation with increasing Φ. After 31 days of storage, the retention index of lutein in the emulsion gel could reach 55.38%, and the corresponding half-life times increased from 12 to 41 days. This study will be useful for designing starch-based Pickering emulsion gel with tunable gel network and desirable characteristics as delivery carrier of sensitive bioactive compounds.

2.
Food Chem ; 306: 125641, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606628

RESUMO

Temperature fluctuation is a common problem in the frozen storage of shrimp products. This study investigated the influence of carrageenan oligosaccharide (CO) and xylooligosaccharide (XO) on the growth and recrystallization of ice crystals in frozen peeled shrimp exposed to temperature fluctuations. Shrimp soaked with water and 3.0% (w/v) Na4P2O7 solution were designated as the negative and positive controls, respectively. Our data revealed that both CO- and XO-soaked shrimp had significant improvements in thawing and cooking loss, myofibrillar protein content, Ca2+-ATPase activity, and textural variables when exposed to temperature fluctuations compared to control samples. Microstructural imaging indicated that soaking the shrimp in CO and XO slowed the progression of damage caused to tissue myofibrils by large ice crystals, as well as inhibited the growth and recrystallization of ice crystals in muscle tissues. SDS-PAGE analysis confirmed that treatment with the oligosaccharides exhibited marked effects on the stability of muscle proteins and inhibited the degradation of muscle proteins affected by the temperature fluctuations. Based on these data, we hypothesize that the incorporated CO and XO may bind to muscle proteins and capture water molecules in the myofibrillar network through hydrogen bonding, thereby suppressing the myofibrillar denaturation and tissue structure destruction induced by the growth and recrystallization of ice crystals.

3.
J Ethnopharmacol ; 247: 112299, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606537

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and realgar (As4S4). The ethnopharmacological basis of cinnabar and realgar in HFD is not known. AIM OF THE STUDY: To address the role of cinnabar and realgar in HFD-produced neuroprotection against neurodegenerative diseases and disturbance of gut microbiota. MATERIALS AND METHODS: Lipopolysaccharide (LPS) plus rotenone (ROT)-elicited rat dopaminergic (DA) neuronal damage loss was performed as a Parkinson's disease animal model. Rats were given a single injection of LPS. Four months later, rats were challenged with the threshold dose of ROT. The clinical dose of HFD was administered via feed, starting from ROT administration for 46 days. Behavioral dysfunction was detected by rotarod and Y-maze tests. DA neuron loss and microglial activation were assessed via immunohistochemical staining and western bolt analysis. The colon content was collected to extract bacterial DNA followed by real-time PCR analysis with 16S rRNA primers. RESULTS: LPS plus ROT induced neurotoxicity, as evidenced by DA neuron loss in substantia nigra, impaired behavioral functions and increased microglial activation. HFD-original (containing 10% cinnabar and 10% realgar) rescued loss of DA neurons, improved behavioral dysfunction and attenuated microglial activation. Compared with HFD-original, HFD-reduced (3% cinnabar and 3% realgar) was also effective, but to be a less extent, while HFD-removed (without cinnabar and realgar) was ineffective. In analysis of gut microbiome, the increased Verrucomicrobiaceae and Lactobacteriaceae, and the decreased Enterobacteeriaceae by LPS plus ROT were ameliorated by HFD-original, and to be the less extent by HFD-reduced. CONCLUSION: Cinnabar and realgar are active ingredients in HFD to exert beneficial effects in a neurodegenerative model and gut microbiota.

4.
J Cell Biochem ; 121(1): 25-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31433522

RESUMO

Myocardial dysfunction is an important manifestation of sepsis. In addition, inactivation of the mitogen-activated protein kinase (MAPK) signaling pathway has been reported to be beneficial in sepsis. The current study used gene expression profiling to demonstrate the overexpression of angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in sepsis. In this study, we used a rat model of sepsis established by cecal ligation and puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed. Enzyme-linked immunosorbent assay was used to measure the concentration of cardiac troponin T (TnT), cardiac troponin I (cTnI), and creatine kinase isoenzyme muscle/brain (CK-MB). Myocardial enzyme, tissue antioxidant capacity, mitochondria swelling, and membrane potential were also detected. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining was applied to measure cell apoptosis, and messenger RNA and protein levels of apoptosis-related proteins (Fas ligand [Fasl], B-cell CLL/lymphoma [Bcl-2], p53) were also detected. Initially, sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of TnT, cTnI, and CK-MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased extracellular signal-regulated kinase and cyclic adenosine 3',5'-monophosphate response element binding protein expression), decreased EF, heart rate, and concentrations of TnT, cTnI, and CK-MB, but increased sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl-2 expression). These findings indicated that AT1R silencing plays an inhibitory role in sepsis-induced myocardial injury by inhibiting the MAPK signaling pathway.

5.
J Comput Chem ; 41(1): 56-68, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31621932

RESUMO

We propose a free energy calculation method for receptor-ligand binding, which have multiple binding poses that avoids exhaustive enumeration of the poses. For systems with multiple binding poses, the standard procedure is to enumerate orientations of the binding poses, restrain the ligand to each orientation, and then, calculate the binding free energies for each binding pose. In this study, we modify a part of the thermodynamic cycle in order to sample a broader conformational space of the ligand in the binding site. This modification leads to more accurate free energy calculation without performing separate free energy simulations for each binding pose. We applied our modification to simple model host-guest systems as a test, which have only two binding poses, by using a single decoupling method (SDM) in implicit solvent. The results showed that the binding free energies obtained from our method without knowing the two binding poses were in good agreement with the benchmark results obtained by explicit enumeration of the binding poses. Our method is applicable to other alchemical binding free energy calculation methods such as the double decoupling method (DDM) in explicit solvent. We performed a calculation for a protein-ligand system with explicit solvent using our modified thermodynamic path. The results of the free energy simulation along our modified path were in good agreement with the results of conventional DDM, which requires a separate binding free energy calculation for each of the binding poses of the example of phenol binding to T4 lysozyme in explicit solvent. © 2019 Wiley Periodicals, Inc.

6.
Talanta ; 207: 120294, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594563

RESUMO

Dual-functional nanosensors based on small molecule regulation can be widely used due to their simplicity, high sensitivity and selectivity. Herein, glutathione (GSH) calibrated dual-functional system for GSH and cadmium ions (Cd2+) detection based on fluorescence resonance energy transfer (FRET) between NH2-NaYF4:Yb,Er/NaYF4@SiO2 upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) is designed. Unmodified AuNPs are easy to aggregate in high-salt solution and thereby quenching the red emission of UCNPs. The presence of GSH prevents the aggregation of AuNPs, so GSH can be detected by the changes in the color of solution and the recovery of red emission of UCNPs. However, Cd2+ can interact with GSH, which makes AuNPs easy to aggregate, resulting in a gradual decrease in red emission of UCNPs. The fluorescence response of the system is linear with the concentrations of GSH and Cd2+ in a wide range of concentrations, with low detection limits of 0.016 µM and 0.059 µM, respectively. Furthermore, the nanosensor demonstrates high selectivity for GSH and Cd2+ detection and can be applied for the detection of GSH in human plasma and Cd2+ in drinking water.

7.
Dev Comp Immunol ; 103: 103529, 2020 Feb.
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 immuneresponses 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.

8.
Environ Pollut ; : 113627, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31796321

RESUMO

Lead (Pb) is one of the predominant heavy metals in e-waste recycling arears and recognized as a notorious environmental neurotoxic substance. However, whether Pb at environmentally relevant concentrations could cause neurobehavioral alteration and even what kind of signaling pathway Pb exposure would disrupt in zebrafish were not fully uncovered. In the present study, 6 h postfertilization (hpf) zebrafish embryos were exposed to Pb at the concentrations of 0, 5, 10, and 20 µg/L until 144 hpf. Then the neurobehavioral indicators including locomotor, turnings and social behaviors, and the expressions of selected genes concerning brain-derived neurotrophic factor (BDNF) signaling were investigated. The results showed that significant changes were obtained under 20 µg/L Pb exposure. The hypoactivity of zebrafish larvae in locomotor and turning behaviors was induced during the dark period, while hyperactivity was observed in a two-fish social assay during the light period. The significantly downregulation of genes encoding BDNF, its receptor TrkB, and N-methyl-D-aspartate glutamate receptor (NMDAR) suggested the involvement of NMDAR-dependent BDNF signaling pathway. Overall, our study demonstrated that developmental exposure to Pb at environmentally relevant concentrations caused obvious neurobehavioral impairment of zebrafish larvae by disrupting the NMDAR-dependent BDNF signaling, which could exert profound ecological consequences in the real environment.

9.
Vet Res ; 50(1): 105, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783919

RESUMO

Outer membrane protein P2 (OmpP2) of the virulent Haemophilus (Glaesserella) parasuis has been shown to induce the release of proinflammatory cytokines. The OmpP2 protein is composed of eight or nine surface-exposed loops, but it is unclear which of them participates in the OmpP2-induced inflammatory response. In this study, we synthesized linear peptides corresponding to surface-exposed loops L1-L8 of OmpP2 from the virulent H. parasuis SC096 strain to stimulate porcine alveolar macrophages (PAMs) in vitro. We found that both L7 and L8 significantly upregulated the mRNA expression of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, IL-17, and IL-23 and the chemokines CCL-4 and CCL-5 in a time- and dose-dependent manner. Additionally, we constructed ompP2ΔLoop7 and ompP2ΔLoop8 mutant SC096 strains and extracted their native OmpP2 proteins to stimulate PAMs. These mutant proteins induced significantly less mRNA expression of inflammatory cytokines than SC096 OmpP2. Next, the amino acid sequences of L7 and L8 from 15 serovars of H. parasuis OmpP2 were aligned. These sequences were relatively conserved among the most virulent reference strains, suggesting that L7 and L8 are the most active peptides of the OmpP2 protein. Furthermore, L7 and L8 significantly upregulated the NF-κB and AP-1 activity levels based on luciferase reporter assays in a dose-dependent manner. Therefore, our results demonstrated that both surface-exposed loops L7 and L8 of H. parasuis OmpP2 induced the expression of proinflammatory cytokines possibly by activating the NF-κB and MAPK signalling pathways in cells infected by H. parasuis.

10.
Biomaterials ; : 119636, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31785776

RESUMO

Sonodynamic therapy (SDT) has rapidly developed as a powerful alternative to traditional photodynamic therapy due to its intrinsically deeper tissue-penetration. However, single SDT dose is incapable of radical cure because the long-term hypoxia of tumor limits its therapeutic effect. Herein, we developed a biomimetic nanoplatform with dual pH/ultrasound response, homologous targeting and low phototoxicity for combined nitric oxide (NO) gas therapy with SDT to solve the problem. This nanoplatform is composed of zeolite imidazole framework-8 material embedded with nitrosoglutathione (GSNO) and chlorin e6 (Ce6) by one-step encapsulation, and then wrapped by homologous tumor cell membrane. In vitro and in vivo experiments indicate that the biomimetic nanoplatform has excellent biocompatibility and shows higher retention in tumor by homologous targeting. Importantly, it can sustainably release the encapsulated drug in acidic tumor microenvironment and accelerate degradation by ultrasound (US). Furthermore, NO released from GSNO and reactive oxygen species generated by Ce6, which are both triggered by US, react with each other to produce highly reactive peroxynitrite to inhibit the growth of tumor. Moreover, by repeated US irradiation, the tumor hypoxia can be relieved for a much-longer term, resulting in an effective gas-sonodynamic combined treatment. This study fully utilizes the advantages of US, providing a new strategy for high-performance cancer therapy.

11.
Ecotoxicology ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784922

RESUMO

Western flower thrips (WFT), Frankliniella occidentalis, has become an important pest of vegetables worldwide, due to its economic damage to crop production. In order to control WFT, chemical insecticides are widely used. However, WFT has developed a high resistance against many kinds of insecticides. Na+, K+-ATPase, playing an important role in the ionic transmission across the membrane, is commonly considered to be the target of several xenobiotic compounds. However, whether the Na+, K+-ATPase can be used as one of the target sites for controlling WFT is still unknown. In this study, resistance levels of WFT to four insecticides (chlorpyrifos, beta cypermethrin, abamectin, and thiamethoxam) were measured. It was found that all four insecticides exhibited significant inhibitory effects on WFT, especially on nymphs. The activity of Na+, K+-ATPase was estimated after the treatment of four insecticides. Additionally, mRNA expression levels of three Na+, K+-ATPase α-subunit isoforms (X1, X2 and X3) were detected using RT-qPCR. The transcription profile of three Na+, K+-ATPase α-subunit isoforms were diverse after treatment by these four insecticides, which indicated that these isoforms might play different roles in the tolerance to insecticides. The results suggested that Na+, K+-ATPase can obviously be inhibited by these four classes of insecticide, and may serve as the new target for controlling WFT.

12.
Glia ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793691

RESUMO

Microglia constantly survey the brain microenvironment and rapidly adopt different phenotypes in response to environmental stimuli. Such dynamic functions require a unique metabolism and bioenergetics. However, little is known about the basic metabolism of microglia and how metabolic changes regulate microglia function. Here, we uncover that microglia activation is accompanied by extensive transcriptional changes in glucose and lipid metabolism-related genes. Using metabolic flux assays, we found that LPS, a prototype of the pathogen-associated molecular patterns (PAMPs), significantly enhanced glycolysis but suppressed oxidative phosphorylation (OXPHOS) in primary cultured microglia. By contrast, ATP, a known damage-associated molecular pattern (DAMPs) that triggers sterile activation of microglia, boosted both glycolysis and OXPHOS. Importantly, both LPS and ATP activated the mechanistic target of rapamycin (mTOR) pathway and enhanced the intracellular reactive oxygen species (ROS). Inhibition of mTOR activity suppressed glycolysis and ROS production in both conditions but exerted different effects on OXPHOS: it attenuated the ATP-induced elevation of OXPHOS, yet had no impact on the LPS-induced suppression of OXPHOS. Further, inhibition of mTOR or glycolysis decreased production of LPS-induced proinflammatory cytokines and ATP-induced tumor necrosis factor-α (TNF-α) and brain derived neurotrophic factor (BDNF) in microglia. Our study reveals a critical role for mTOR in the regulation of metabolic programming of microglia to shape their distinct functions under different states and shed light on the potential application of targeting metabolism to interfere with microglia-mediated neuroinflammation in multiple disorders.

13.
Sci Rep ; 9(1): 17262, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754257

RESUMO

Photoacoustic imaging has the advantages of high contrast and deep imaging depth. However, with the increasing of imaging depth, the signal-to-noise ratio (SNR) of the detected signal decreases, due to the light scattering that seriously affects the recovery image quality. In this paper, we experimentally demonstrated that higher contrast photoacoustic imaging was achieved using photoacoustic wavefront shaping technology in the presence of light scattering and low SNR signals. The imaging contrast is improved from 1.51 to 5.30. More importantly, we propose a dynamic time window method for the photoacoustic signal extraction algorithm, named correlation detection of adaptive time window, which further improves the contrast of photoacoustic imaging to 9.57. Our method effectively improves the contrast of photoacoustic imaging through scattering media.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31755739

RESUMO

Background: Colorectal cancer (CRC) is considered as one of the most lethal malignancies worldwide. However, the effective therapies remain limited. Polydatin, a main effective component of the Chinese herb Polygonum cuspidatum, has multiple antitumor activities; however, whether Polydatin has anti-CRC activity is not fully understood. Materials and Methods: CRC cell proliferation and apoptosis were measured after treatment of Polydatin using Cell Counting Kit-8 assay, colony formation assay, and flow cytometer assay. The expression of miR-382 and programmed cell death ligand 1 (PD-L1) were determined in CRC cell lines by quantitative real-time polymerase chain reaction and western blot, respectively. Furthermore, dual-luciferase reporter assay was conducted to determine the target of miR-382. Moreover, loss-of-functional experiments were used to identify the effect of Polydatin on miR-382. Finally, tumor xenograft experiments were conducted to determine the effect of Polydatin in vivo. Results: As a result, Polydatin effectively inhibited cell proliferation and promoted cell apoptosis in CRC cell lines. PD-L1 was confirmed as a direct target of miR-382. Furthermore, Polydatin could suppress the expression of PD-L1 by upregulating miR-382. Moreover, Polydatin inhibits proliferation and promotes apoptosis of CRC cells by regulating miR-382 and suppressing CRC tumor growth in vivo. Conclusion: Polydatin inhibits CRC cell proliferation and promotes apoptosis by regulating miR-382/PD-L1 axis. Polydatin could be a potential compound to synthesize novel antitumor drugs.

15.
Stem Cells ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721356

RESUMO

Mesenchymal stem cells (MSCs), which are undifferentiated stem cells with the property of stemness and the potential to differentiate into multiple lineages, including osteoblasts, have attracted a great deal of attention in bone tissue engineering. Consistent with the heterogeneity of MSCs, various surface markers have been used. However, it is still unclear which markers of MSCs are best for cell amplification in vitro and later bone regeneration in vivo. Krüppel-like Factor 2 (KLF2) is an important indicator of the stemness of hMSCs [1], and as early vascularization is also critical for bone regeneration, we used KLF2 as a novel in vitro marker for MSCs and investigated the angiogenesis and osteogenesis between KLF2+ MSCs and endothelial cells (ECs). We found a synergistic interaction between hMSCs and human umbilical vein ECs (HUVECs) in that KLF2+ stemness-maintained hMSCs initially promoted the angiogenesis of HUVECs, which in turn more efficiently stimulated the osteogenesis of hMSCs. In fact, KLF2+ hMSCs secreted angiogenic factors initially, with some of the cells then differentiating into pericytes through the PDGF-BB/PDGFR-ß signaling pathway, which improved blood-vessel formation. The matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through upregulated vascular endothelial growth factor (VEGF). A three-dimensional (3D) coculture model using cell-laden GelMA hydrogel further confirmed these results. This study provides insight into the stemness-directed synergistic interaction between hMSCs and HUVECs, and our results will have a profound impact on further strategies involving the application of KLF2+ hMSC/HUVEC-laden GelMA hydrogel in vascular network bioengineering and bone regeneration. © AlphaMed Press 2019 SIGNIFICANCE STATEMENT: KLF2 was creatively put forward as a novel marker in vitro for MSCs to investigate the osteogenesis and angiogenesis between KLF2+ MSCs and ECs. We demonstrated there was a synergistic strategy to help readers understand the process of intercellular interaction between hMSCs and HUVECs, which KLF2+ hMSCs secreted angiogenic factors like ANG1 initially, and some of hMSCs then differentiated into pericytes through PDGF-BB/PDGFR-ß signaling pathway. Both of which improved the formation of blood vessels. Matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through the up-regulated VEGF more efficiently. This work therefore focuses on the synergistic strategy between KLF2+ hMSCs and HUVECs and will have a profound impact on further vascular network bioengineering and bone regeneration.

16.
Medicine (Baltimore) ; 98(44): e17740, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689822

RESUMO

To identify independent factors associated with prolonged hospital length of stay (LOS) in elderly patients undergoing first-time elective open posterior lumbar fusion surgery.We retrospectively analyzed the data of 303 elderly patients (age range: 60-86 years) who underwent first-time elective open lumbar posterior fusion surgery at our center from December 2012 to December 2017. Preoperative and perioperative variables were extracted and analyzed for all patients, and multivariate stepwise regression analysis was used to determine the variables affecting the LOS and important predictors of LOS prolongation (P < .001).The mean age of the patients was 67.0 ±â€Š5.5 years, and the mean LOS was 18.5 ±â€Š11.8 days, ranging from 7 to 103 days. Of the total, 166 patients (54.8%) were men and 83 patients (27.4%) had extended LOS. Multiple linear regression analysis determined that age (P < .001), preoperative waiting time ≥7 days (P < .001), pulmonary comorbidities (P = .010), and diabetes (P = .010) were preoperative factors associated with LOS prolongation. Major complications (P = .002), infectious complications (P = .001), multiple surgeries (P < .001), and surgical bleeding (P = .018) were perioperative factors associated with LOS prolongation. Age (P < .001), preoperative waiting time ≥7 days (P < .001), infectious complications (P < .001), and multiple surgeries (P < .001) were important predictors of LOS prolongation.Extended LOS after first-time elective open posterior lumbar fusion surgery in elderly patients is associated with factors including age, preoperative waiting time, infectious complications, and multiple surgeries. Surgeons should recognize and note these relevant factors while taking appropriate precautions to optimize the modifiable factors, thereby reducing the LOS as well as hospitalization costs.


Assuntos
Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Fusão Vertebral/estatística & dados numéricos , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Listas de Espera
17.
J Chem Theory Comput ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31756104

RESUMO

Intrinsically disordered proteins (IDPs) constitute a significant fraction of eukaryotic proteomes. High-resolution characterization of IDP conformational ensembles can help elucidate their roles in a wide range of biological processes but remains challenging both experimentally and computationally. Here, we present a generic algorithm to improve the accuracy of coarse-grained IDP models using a diverse set of experimental measurements. It combines maximum entropy optimization and least squares regression to systematically adjust model parameters and improve the agreement between simulation and experiment. We successfully applied the algorithm to derive a transferable force field, which we term as MOFF, for de novo prediction of IDP structures. Statistical analysis of force field parameters reveals features of amino acid interactions not captured by potentials designed to work well for folded proteins. We anticipate its combination of efficiency and accuracy will make MOFF useful for studying the phase separation of IDPs, which drives the formation of various biological compartments.

18.
PLoS Genet ; 15(10): e1008460, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31671093

RESUMO

Malfunction of pre-mRNA processing factors are linked to several human diseases including cancer and neurodegeneration. Here we report the identification of a de novo heterozygous missense mutation in the SNRPE gene (c.65T>C (p.Phe22Ser)) in a patient with non-syndromal primary (congenital) microcephaly and intellectual disability. SNRPE encodes SmE, a basal component of pre-mRNA processing U snRNPs. We show that the microcephaly-linked SmE variant is unable to interact with the SMN complex and as a consequence fails to assemble into U snRNPs. This results in widespread mRNA splicing alterations in fibroblast cells derived from this patient. Similar alterations were observed in HEK293 cells upon SmE depletion that could be rescued by the expression of wild type but not mutant SmE. Importantly, the depletion of SmE in zebrafish causes aberrant mRNA splicing alterations and reduced brain size, reminiscent of the patient microcephaly phenotype. We identify the EMX2 mRNA, which encodes a protein required for proper brain development, as a major mis-spliced down stream target. Together, our study links defects in the SNRPE gene to microcephaly and suggests that alterations of cellular splicing of specific mRNAs such as EMX2 results in the neurological phenotype of the disease.

20.
Environ Int ; 134: 105282, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711017

RESUMO

BACKGROUND: Experimental studies have demonstrated that cadmium exposure induces alterations on immune function, but epidemiological evidence is lacking. OBJECTIVE: To examine the associations between prenatal and postnatal cadmium exposure and cellular immune responses among pre-school children. METHODS: Pre-school aged children (n = 407) were followed from a prospective birth cohort study in Wuhan, China. Maternal urinary and children's plasma cadmium concentrations were measured as biomarkers of prenatal and postnatal cadmium exposure, respectively. Children's cellular immune responses were assessed by peripheral blood T lymphocyte subsets and plasma cytokines. Multivariable adjusted models were applied to estimate the associations of prenatal and postnatal cadmium exposure with T lymphocyte subsets and cytokines, and the effect modification by child gender were also examined. RESULTS: Maternal urinary cadmium was associated with reduced absolute counts of CD3+CD4+ cells (-12.45%; 95% CI: -23.74%, 0.40% for the highest vs. lowest quartile; p for trend = 0.045). Inverse associations of maternal urinary cadmium with %CD3+CD4+ cells and CD4+/CD8+ ratio were only observed among females (both p-interaction < 0.050); whereas an inverse association with absolute counts of CD3+CD8+ cells was only observed among males (p-interaction = 0.057). Positive associations of maternal urinary cadmium with %CD3+CD4+ cells, interleukin-4 (IL-4), and IL-6 were only observed among females, although there were no significant interactions. We observed no clear associations of children's plasma cadmium with T lymphocyte subsets and cytokines. CONCLUSION: Prenatal but not postnatal cadmium exposure was associated with sex-specific alterations on children's cellular immune responses.

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