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1.
Hematol Oncol ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34796518

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Most patients with T-ALL are treated with high-dose multi-agent chemotherapy due to limited targeted therapeutic options. To further investigate its pathogenesis and establish new therapeutic targets, we studied the role of FAPP2, a Golgi protein, that is, highly expressed in T-ALL, in the growth and function of T-ALL. We found that T-ALL cells underwent reduced cell proliferation and sub-G1 accumulation after knocking down of FAPP2 gene using shRNA systems. Instead, FAPP2 downregulation promoted cell autophagy. The level of autophagy markers, LC3Ⅱ/Ⅰ, Beclin1, and ATG5, was markedly increased, whereas that of P62 decreased after FAPP2 knocking down in T-ALL cells. FAPP2 knocking down led to the accumulation of LC3 in the cytoplasm of T-ALL cells as shown by fluorescence microscopy. In addition, the level of PI(4)P and PI(3,4,5)P decreased and phosphorylation of P-AKT and P-mTOR were downregulated in FAPP2 knock-down cells. In summary, our results show that decreased expression of FAPP2 inhibited cell proliferation, resulted in the sub-G1 phase accumulation of T-ALL cells, and enhanced autophagy of T-ALL cells, likely mediated by PI(4)P, PI(3,4,5)P, and PI3K/AKT/mTOR pathway. Our results provide a new insight into the pathogenesis and development of potential targeted therapy of T-ALL.

2.
Curr Opin Plant Biol ; 65: 102144, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34823206

RESUMO

The maternal-to-zygotic transition (MZT) is a major developmental transition in the life cycles of animals. It consists of two associated processes: maternal transcript clearance and zygotic genome activation (ZGA). The concept of MZT has been controversially discussed in plants. In this short review, we summarize recent advances in understanding the timing of ZGA and the similarities and differences between ZGA in eudicots and monocots. We discuss the parental contributions to the transcriptome of the proembryo and parental control of early embryogenesis, and we examine distinct differences in the ZGA between animals and plants, update relevant concepts on MZT, and highlight outstanding questions in this field.

3.
Foods ; 10(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34829056

RESUMO

Detection of copper (II) ions (Cu2+) in water is important for preventing them from entering the human body to preserve human health. Here, a highly sensitive and selective fluorescence probe that uses mercaptopropionic acid (MPA)-capped InP/ZnS quantum dots (MPA-InP/ZnS QDs) was proposed for the detection of trace amounts of Cu2+ in water. The fluorescence of MPA-InP/ZnS QDs can be quenched significantly in the presence of Cu2+, and the fluorescence intensity shows excellent linearity when the concentration of Cu2+ varies from 0-1000 nM; this probe also exhibits an extremely low limit of detection of 0.22 nM. Furthermore, a possible fluorescence-quenching mechanism was proposed. The MPA-InP/ZnS QDs probes were further applied to the detection of trace Cu2+ in real water samples and drink samples, showing good feasibility.

4.
Eye Vis (Lond) ; 8(1): 38, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666831

RESUMO

PURPOSE: We investigated the effects of retinal ischemia, neurodegeneration, and subclinical edema on best-corrected visual acuity (BCVA) in the early stages of diabetic retinopathy (DR). METHODS: Ischemia was evaluated by the microvascular parameters measured by optical coherence tomography angiography. Neurodegeneration and subclinical edema were identified by the intraretinal layer thickness obtained by optical coherence tomography. Eyes with nonproliferative diabetic retinopathy (n = 132) from 89 patients were analyzed. Eyes were classified as having normal BCVA (n = 88 [66.7%], Snellen equivalent ≥ 20/20) or decreased BCVA (n = 44 [33.3%], Snellen equivalent < 20/20). The prevalence of ischemia, neurodegeneration, and subclinical edema was explored in patients with and without decreased BCVA, and correlations between BCVA and these pathological pathways were determined. RESULTS: Vessel density in the deep retinal capillary plexus (DRCP) and thickness of ganglion cell layer plus inner plexiform layer (GCL-IPL) were significantly lower in eyes with decreased BCVA compared with eyes with normal BCVA (both P < 0.05). In the final multiple regression predictive model, age, DRCP vessel density, and GCL-IPL thickness (all P ≤ 0.044) were predictors of BCVA. DRCP vessel density and GCL-IPL thickness have an interactive effect on visual acuity. The proportions of ischemia and neurodegeneration were significantly higher in eyes with decreased BCVA than in eyes with normal BCVA (P = 0.001 and P = 0.004, respectively). CONCLUSION: During the natural course of the early stages of DR, ischemia and neurodegeneration were the main disease pathways associated with visual acuity, and the mechanisms varied among patients.

5.
Front Immunol ; 12: 702425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489952

RESUMO

Antiphospholipid syndrome (APS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. This clinical phenotype heterogeneity may result in differences in response to treatment and prognosis. In this study, we aimed to identify primary thrombotic APS (TAPS) from primary obstetric APS (OAPS) using urine proteomics as a non-invasive method. Only patients with primary APS were enrolled in this study from 2016 to 2018 at a single clinical center in Shanghai. Urine samples from 15 patients with TAPS, 9 patients with OAPS, and 15 healthy controls (HCs) were collected and analyzed using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis to identify differentially expressed proteins. Cluster analysis of urine proteomics identified differentiated proteins among the TAPS, OAPS, and HC groups. Urinary proteins were enriched in cytokine and cytokine receptor pathways. Representative secreted cytokines screened out (fold change >1.20, or <0.83, p<0.05) in these differentiated proteins were measured by enzyme-linked immunosorbent assay in a validation cohort. The results showed that the levels of C-X-C motif chemokine ligand 12 (CXCL12) were higher in the urine of patients with TAPS than in those with OAPS (p=0.035), while the levels of platelet-derived growth factor subunit B (PDGFB) were lower in patients with TAPS than in those with OAPS (p=0.041). In addition, correlation analysis showed that CXCL12 levels were positively correlated with immunoglobulin G anti-ß2-glycoprotein I antibody (r=0.617, p=0.016). Our results demonstrated that urinary CXCL12 and PDGFB might serve as potential non-invasive markers to differentiate primary TAPS from primary OAPS.

6.
Pattern Recognit ; 1202021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34421131

RESUMO

Accurate segmentation of corneal layers depicted on optical coherence tomography (OCT) images is very helpful for quantitatively assessing and diagnosing corneal diseases (e.g., keratoconus and dry eye). In this study, we presented a novel boundary-guided convolutional neural network (CNN) architecture (BG-CNN) to simultaneously extract different corneal layers and delineate their boundaries. The developed BG-CNN architecture used three convolutional blocks to construct two network modules on the basis of the classical U-Net network. We trained and validated the network on a dataset consisting of 1,712 OCT images acquired on 121 subjects using a 10-fold cross-validation method. Our experiments showed an average dice similarity coefficient (DSC) of 0.9691, an intersection over union (IOU) of 0.9411, and a Hausdorff distance (HD) of 7.4423 pixels. Compared with several other classical networks, namely U-Net, Attention U-Net, Asymmetric U-Net, BiO-Net, CE-Net, CPFnte, M-Net, and Deeplabv3, on the same dataset, the developed network demonstrated a promising performance, suggesting its unique strength in segmenting corneal layers depicted on OCT images.

7.
J Chromatogr A ; 1654: 462454, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34407469

RESUMO

Continuous chromatography is a promising technology for downstream processing of biopharmaceuticals. The operation of continuous processes is significantly different to batch-mode chromatography and needs comprehensive evaluation. In this work, the performances of four Protein A affinity resins were studied systematically for twin-column continuous capture processes. A model-based approach was used to evaluate the process performance (productivity and capacity utilization) under varying operation conditions, and the objective was to reveal the crucial resin properties for continuous capture. The trade-off between productivity and capacity utilization was found, and it is necessary to select appropriate resins for different feedstock and operation conditions. The capacity utilization heavily depends on mass transfer, and steep breakthrough curves are favorable for high capacity utilization. The productivity is determined by both equilibrium binding capacity and mass transfer, and the balance of feed amount and feed time is critical. Moreover, the influence of binding capacity and mass transfer on process productivity and parameter sensitivity with two important resin properties (equilibrium binding capacity qmax and effective pore diffusion coefficient De) were assessed by the model, and suitable resin parameter ranges for twin-column continuous capture were determined. The model-based approach is an effective and useful tool to evaluate the complex performance of different resins and guide the design of next-generation resins for continuous processes.


Assuntos
Cromatografia de Afinidade , Proteína Estafilocócica A , Cromatografia de Afinidade/instrumentação , Cromatografia de Afinidade/normas , Modelos Químicos , Proteína Estafilocócica A/metabolismo
8.
Sci Bull (Beijing) ; 66(22): 2312-2319, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34336365

RESUMO

The presence of antiphospholipid antibodies was shown to be associated with thrombosis in coronavirus disease 2019 (COVID-19) patients. Recently, according to reports from several studies, the vaccine-induced immune thrombotic thrombocytopenia is mediated by anti-platelet factor 4 (PF4)-polyanion complex in adenovirus-vectored COVID-19 vaccine recipients. It is impendent to explore whether inactivated COVID-19 vaccine widely used in China influences prothrombotic autoantibody production and induces thrombosis. In this prospective study, we recruited 406 healthcare workers who received two doses, 21 days apart, of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBP-CorV, Sinopharm). Paired blood samples taken before vaccination and four weeks after the second vaccination were used in detecting prothrombotic autoantibodies, including anticardiolipin (aCL), anti-ß2 glycoprotein I (aß2GP1), anti-phosphatidylserine/prothrombin (aPS/PT), and anti-PF4-heparin. The seroconversion rate of SARS-CoV-2 specific antibodies was 95.81% (389/406) four weeks after vaccination. None of the subjects had spontaneous thrombosis or thrombocytopenia over a minimum follow-up period of eight weeks. There was no significant difference in the presence of all ten autoantibodies between samples collected before and after vaccination: for aCL, IgG (7 vs. 8, P = 0.76), IgM (41 vs. 44, P = 0.73), IgA (4 vs. 4, P = 1.00); anti-ß2GP1, IgG (7 vs. 6, P = 0.78), IgM (6 vs. 5, P = 0.76), IgA (3 vs. 5, P = 0.72); aPS/PT IgG (0 vs. 0, P = 1.00), IgM (6 vs. 5, P = 0.76); aPF4-heparin (2 vs. 7, P = 0.18), and antinuclear antibody (ANA) (18 vs. 21, P = 0.62). Notably, seven cases presented with anti-PF4-heparin antibodies (range: 1.18-1.79 U/mL) after vaccination, and none of them exhibited any sign of thrombotic disorder. In conclusion, inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibody and anti-PF4-heparin antibody nor increase the risk of thrombosis.

9.
Eng Life Sci ; 21(6): 382-391, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34140849

RESUMO

Downstream processing of mAb charge variants is difficult owing to their similar molecular structures and surface charge properties. This study aimed to apply a novel twin-column continuous chromatography (called N-rich mode) to separate and enrich acidic variants of an IgG1 mAb. Besides, a comparison study with traditional scaled-up batch-mode cation exchange (CEX) chromatography was conducted. For the N-rich process, two 3.93 mL columns were used, and the buffer system, flow rate and elution gradient slope were optimized. The results showed that 1.33 mg acidic variants with nearly 100% purity could be attained after a 22-cycle accumulation. The yield was 86.21% with the productivity of 7.82 mg/L/h. On the other hand, for the batch CEX process, 4.15 mL column was first used to optimize the separation conditions, and then a scaled-up column of 88.20 mL was used to separate 1.19 mg acidic variants with the purity of nearly 100%. The yield was 59.18% with the productivity of 7.78 mg/L/h. By comparing between the N-rich and scaled-up CEX processes, the results indicated that the N-rich method displays a remarkable advantage on the product yield, i.e. 1.46-fold increment without the loss of productivity and purity. Generally, twin-column N-rich continuous chromatography displays a high potential to enrich minor compounds with a higher yield, more flexibility and lower resin cost.

10.
Environ Pollut ; 287: 117615, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34171732

RESUMO

Mean oceanic CO2 values have already risen and are expected to rise further on a global scale. Elevated pCO2 (eCO2) changes the bacterial community in seawater. However, the ecological association of seawater microbiota and related geochemical functions are largely unknown. We provide the first evidence that eCO2 alters the interaction patterns and functional potentials of microbiota in rearing seawater of the swimming crab, Portunus trituberculatus. Network analysis showed that eCO2 induced a simpler and more modular bacterial network in rearing seawater, with increased negative associations and distinct keystone taxa. Using the quantitative microbial element cycling method, nitrogen (N) and phosphorus (P) cycling genes exhibited the highest increase after one week of eCO2 stress and were significantly associated with keystone taxa. However, the functional potential of seawater bacteria was decoupled from their taxonomic composition and strongly coupled with eCO2 levels. The changed functional potential of seawater bacteria contributed to seawater N and P chemistry, which was highlighted by markedly decreased NH3, NH4+-N, and PO43--P levels and increased NO2--N and NO3--N levels. This study suggests that eCO2 alters the interaction patterns and functional potentials of seawater microbiota, which lead to the changes of seawater chemical parameters. Our findings provide new insights into the mechanisms underlying the effects of eCO2 on marine animals from the microbial ecological perspective.


Assuntos
Dióxido de Carbono , Microbiota , Animais , Bactérias/genética , Nitrogênio , Água do Mar
11.
Endocr J ; 68(10): 1197-1208, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34039781

RESUMO

Reduced bone formation in patients with T-cell acute lymphoblastic leukemia (T-ALL) may be related to the interaction between tumour cells and bone marrow stromal cells (BMSCs). The miRNAs in extracellular vesicles derived from leukemia cells play an essential role in regulating the function of BMSCs; however, the regulatory mechanisms remain unclear. The expression of miR-34a-5p in T-ALL patients and cells was measured by quantitative real-time PCR. BMSCs were co-cultured with extracellular vesicles isolated from T-ALL cells in mineralization medium. The osteogenic differentiation of BMSCs was evaluated by Alizarin Red S staining, alkaline phosphatase (ALP) staining, and detection of osteogenic differentiation markers. A dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-34a-5p and Wnt family member 1 (WNT1). MiR-34a-5p expression was upregulated in T-ALL patients and Jurkat cells. After BMSCs were co-cultured with extracellular vesicles derived from T-ALL cells, osteogenic differentiation of BMSCs was inhibited, and bone mineralization and ALP activity were decreased compared to those of control cells. MiR-34a-5p knockdown in T-ALL cells restored osteogenic differentiation of BMSCs co-cultured with extracellular vesicles. In addition, miR-34a-5p targets and negatively regulates WNT1 expression. In conclusion, our results demonstrated that knockdown of miR-34a-5p in extracellular vesicles derived from T-ALL cells promoted osteogenic differentiation of BMSCs by regulating WNT1.

12.
Nature ; 592(7854): 433-437, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33790463

RESUMO

Upon gamete fusion, animal egg cells secrete proteases from cortical granules to establish a fertilization envelope as a block to polyspermy1-4. Fertilization in flowering plants is more complex and involves the delivery of two non-motile sperm cells by pollen tubes5,6. Simultaneous penetration of ovules by multiple pollen tubes (polytubey) is usually avoided, thus indirectly preventing polyspermy7,8. How plant egg cells regulate the rejection of extra tubes after successful fertilization is not known. Here we report that the aspartic endopeptidases ECS1 and ECS2 are secreted to the extracellular space from a cortical network located at the apical domain of the Arabidopsis egg cell. This reaction is triggered only after successful fertilization. ECS1 and ECS2 are exclusively expressed in the egg cell and transcripts are degraded immediately after gamete fusion. ECS1 and ESC2 specifically cleave the pollen tube attractor LURE1. As a consequence, polytubey is frequent in ecs1 ecs2 double mutants. Ectopic secretion of these endopeptidases from synergid cells led to a decrease in the levels of LURE1 and reduced the rate of pollen tube attraction. Together, these findings demonstrate that plant egg cells sense successful fertilization and elucidate a mechanism as to how a relatively fast post-fertilization block to polytubey is established by fertilization-induced degradation of attraction factors.


Assuntos
Arabidopsis/metabolismo , Endopeptidases/metabolismo , Fertilização , Óvulo Vegetal/metabolismo , Tubo Polínico/metabolismo , Pólen/metabolismo , Arabidopsis/citologia , Arabidopsis/enzimologia , Proteínas de Arabidopsis/metabolismo , Fusão Celular , Óvulo Vegetal/enzimologia , Pólen/enzimologia
13.
ACS Appl Mater Interfaces ; 13(10): 12501-12508, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33683097

RESUMO

An optical organic vapor sensor array based on colorimetric or fluorescence changes quantified by spectroscopy provides an efficient method for realizing rapid identification and detection of organic vapor, but improving the sensitivity of the optical organic vapor sensor is challenging. Here, AIE/polymer (AIE, ggregation-induced emission) composites into microwires arrays are fabricated as organic vapor sensors with specific recognition and high sensitivity for different vapors using the capillary-bridge-mediated assembly method. Such organic vapor sensor successfully detects organic vapor relying on a swelling-induced fluorescence change of the AIE/polymer composites, combating the unique property of AIE molecules and vapor absorption-induced polymer swelling. A series of AIE/polymer composites into microwires arrays with four different groups on the AIE molecule and four different side chains on the polymer is fabricated to detect four different organic vapors. The mechanism for improved sensitivity of the AIE/polymer composites microwires arrays sensors is the same because of the similar polarity between the group of AIE molecules and the vapor molecules. Molecular design of the side chains of the polymer and the groups of AIE molecules based on the polarity of the targeted vapor molecule can enhance the sensitivity of the sensors to the subparts per million level.

14.
Mater Sci Eng C Mater Biol Appl ; 122: 111932, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33641923

RESUMO

Titanium implantation is widely used for dental replacement with advantages of excellent mechanical strength, corrosion resistance, chemical stability and biocompatibility. Some patients, however, are subject to the failure of implantation due to bone resorption, which closely related to the inflammatory responses without clear mechanisms. In this study, first we found that there were inflammatory responses and increases of osteoclasts in the surrounding tissues near by the titanium implant. Further, data revealed that the C3 was increased in the serum and surrounding tissues near by the titanium implant, and activated by classical and alternative pathways. Next, we recognized that the C3a/C3aR, no C3b played an important role in stimulating secretions of pro-inflammatory cytokines of TNF-α and MMP9 via transcription factors NF-kB and NFATc1. This cascade of responses to titanium implant leaded the differentiation and proliferation of osteoclasts in vivo and in vitro, bone resorption of surrounding tissues of Ti implant. These suggest that the cleaved C3a fragment plays predominant roles in the activation of osteoclast. Therefore, the blocking C3a activation should provide potential to prevent bone resorption and prolong the survival of biomaterial implants.


Assuntos
Reabsorção Óssea , Osteoclastos , Diferenciação Celular , Complemento C3a , Humanos , Titânio
15.
Front Microbiol ; 12: 631730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643260

RESUMO

Fungal spoilage of dairy products is a major concern due to food waste and economical losses, some fungal metabolites may furthermore have adverse effects on human health. The use of lactic acid bacteria (LAB) is emerging as a potential clean label alternative to chemical preservatives. Here, our aim was to characterize the growth potential at three storage temperatures (5, 16, and 25°C) of a panel of molds (four Mucor and nine Penicillium strains) isolated from dairy products, then investigate the susceptibility of the molds toward 12 LAB cultures. Fungal cell growth and morphology in malt extract broth was monitored using oCelloScope at 25°C for 24 h. Mucor plumbeus 01180036 was the fastest growing and Penicillium roqueforti ISI4 (P. roqueforti ISI4) the slowest of the tested molds. On yogurt-agar plates, all molds grew at 5, 16, and 25°C in a temperature-dependent manner with Mucor strains growing faster than Penicillium strains regardless of temperature. The sensitivity toward 12 LAB cultures was tested using high-throughput overlay method and here all the molds except P. roqueforti ISI4 were strongly inhibited. The antifungal action of these LAB was confirmed when spotting mold spores on agar plates containing live cells of the LAB strains. However, if cells were removed from the fermentates, the inhibitory effects decreased markedly. The antifungal effects of volatiles tested in a plate-on-plate system without direct contact between mold and LAB culture media were modest. Some LAB binary combinations improved the antifungal activity against the growth of several molds beyond that of single cultures in yogurt serum. The role of competitive exclusion due to manganese depletion was examined as a possible antifungal mechanism for six Penicillium and two Mucor strains. It was shown that this mechanism was a major inhibition factor for the molds tested apart from the non-inhibited P. roqueforti ISI4 since addition of manganese with increasing concentrations of up to 0.1 mM resulted in partly or fully restored mold growth in yogurt. These findings help to understand the parameters influencing the mold spoilage of dairy products and the interactions between the contaminating strains, substrate, and bioprotective LAB cultures.

16.
Theranostics ; 11(10): 4599-4615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754016

RESUMO

HBO1 (KAT7 or MYST2) is a histone acetyltransferase that acetylates H3 and H4 histones. Methods: HBO1 expression was tested in human OS tissues and cells. Genetic strategies, including shRNA, CRISPR/Cas9 and overexpression constructs, were applied to exogenously alter HBO1 expression in OS cells. The HBO1 inhibitor WM-3835 was utilized to block HBO1 activation. Results: HBO1 mRNA and protein expression is significantly elevated in OS tissues and cells. In established (MG63/U2OS lines) and primary human OS cells, shRNA-mediated HBO1 silencing and CRISPR/Cas9-induced HBO1 knockout were able to potently inhibit cell viability, growth, proliferation, as well as cell migration and invasion. Significant increase of apoptosis was detected in HBO1-silenced/knockout OS cells. Conversely, ectopic HBO1 overexpression promoted OS cell proliferation and migration. We identified ZNF384 (zinc finger protein 384) as a potential transcription factor of HBO1. Increased binding between ZNF384 and HBO1 promoter was detected in OS cell and tissues, whereas ZNF384 silencing via shRNA downregulated HBO1 and produced significant anti-OS cell activity. In vivo, intratumoral injection of HBO1 shRNA lentivirus silenced HBO1 and inhibited OS xenograft growth in mice. Furthermore, growth of HBO1-knockout OS xenografts was significantly slower than the control xenografts. WM-3835, a novel and high-specific small molecule HBO1 inhibitor, was able to potently suppressed OS cell proliferation and migration, and led to apoptosis activation. Furthermore, intraperitoneal injection of a single dose of WM-3835 potently inhibited OS xenograft growth in SCID mice. Conclusion: HBO1 overexpression promotes OS cell growth in vitro and in vivo.


Assuntos
Apoptose/genética , Neoplasias Ósseas/genética , Proliferação de Células/genética , Histona Acetiltransferases/genética , Osteossarcoma/genética , Animais , Apoptose/efeitos dos fármacos , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Inibidores Enzimáticos/farmacologia , Feminino , Técnicas de Inativação de Genes , Histona Acetiltransferases/antagonistas & inibidores , Humanos , Masculino , Camundongos , Camundongos SCID , Transplante de Neoplasias , Oncogenes , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Transativadores/metabolismo
17.
Biotechnol Bioeng ; 118(9): 3420-3434, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33755192

RESUMO

The increasing demand for efficient and robust processes in the purification of monoclonal antibodies (mAbs) has recently brought frontal chromatography to the forefront. Applied during the polishing step, it enables the removal of high molecular weight aggregates from the target product, achieving high purities. Typically, this process is operated in batch using a single column, which makes it intrinsically subjected to a purity-yield tradeoff. This means that high purities can only be achieved at the cost of lowering the product yield and vice versa. Recently, a two-column continuous implementation of frontal chromatography, referred to as Flow2, was developed. Despite being able of alleviating the purity-yield tradeoff typical of batch operations, the increase in the number of process parameters complicates its optimal design, with the risk of not exploiting its full potential. In this study, we developed an ad hoc design procedure (DP) suitable for the optimization of both batch frontal chromatography and Flow2 in terms of purity, yield, and productivity. This procedure provided similar results as a multiobjective optimization based on genetic algorithm but with lower computational effort. Then, batch and Flow2 operated at their optimal conditions were compared. Besides showing a more favorable Pareto front of yield and productivity at a specified purity, the Flow2 process demonstrated improved robustness compared to the batch process with respect to modifications in the loading linear velocity, washing buffer ionic strength and loading time, thus providing an appealing operation for integrated processes.

18.
Pain Res Manag ; 2021: 6657463, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33532011

RESUMO

Introduction: "U" route transforaminal percutaneous endoscopic lumbar discectomy (PELD) was introduced for lumbar spinal stenosis (LSS) combined with disc herniation (DH) treatment. This study aims to explore the efficacy and safety of "U" route PELD on chronic pain patients with LSS combined with DH. Methods: Degenerative LSS combined with DH patients who underwent "U" route PELD were reexamined, and 80 patients were recruited and followed up for 2 years. The other 80 healthy individuals who were age- and sex-matched to the patients without chronic pain were enrolled as healthy controls. Minimum dura sac cross-sectional area (mDCSA) by MRI, Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and modified MacNab outcomes were assessed. Emotional evaluation of pain catastrophizing and depression was documented with Pain Catastrophizing Scale (PCS) and Beck Depression Inventory (BDI), respectively, for patients before and after surgery and healthy individuals. Results: All patients were of the age range from 47 to 85 years, with an average of 59.5 ± 9.76 years. Symptoms duration was 114.6 ± 22.77 months, operation time was 87.7 ± 25.20 minutes, and the average hospital stay was 5.8 ± 2.81 days. Four patients quit, and hence, a total of 76 patients completed the follow-up. The results indicated that mDCSA was improved significantly after operation (p < 0.001), either low back and leg VAS or ODI decreased over time (p < 0.001), and the excellent-to-good rate was improved from 88.75% to 93.42% during postoperative 2 years (p < 0.05). Complications of dural tear, nerve root, or dysesthesia were reported in 5 patients, and all recovered after conservative therapy. The scores of pain catastrophizing were reduced after operation (p < 0.001), but no significance of BDI was found between patients and healthy controls (p > 0.05). Conclusions: The "U" route PELD seems an alternative to LSS combined with DH treatment, which might reach a better decompression and effectively improve chronic pain conditions. Still, the complications were potential and required further consideration.


Assuntos
Dor Crônica/etiologia , Dor Crônica/terapia , Discotomia Percutânea/métodos , Discotomia/métodos , Endoscopia/métodos , Estenose Espinal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estenose Espinal/patologia , Resultado do Tratamento
19.
J Sci Food Agric ; 101(12): 4987-4994, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33543483

RESUMO

BACKGROUND: Many new forecasting models have been applied to fish freshness prediction like support vector regression (SVR) and radial basis function neural network (RBFNN). In this study, RBFNN, SVR, and Arrhenius models were established and compared for predicting and evaluating the quality of salmon fillets during storage at different temperatures, based on thiobarbituric acid (TBA), total volatile basic nitrogen (TVB-N), total viable counts (TVCs), K value, and sensory assessment (SA). RESULTS: The TBA, TVB-N, TVC, and K values increased during storage whereas SA decreased. Residuals of the three models are random and irregular, indicating that these models were suitable for predicting the freshness of salmon fillets. The RBFNN predicted quality of salmon fillets stored at different temperatures with relative errors all within ±5% (except for the TVC value at day 6). Relative errors of the SVR model for predicting TVB-N and K value were within 10%, while the relative errors of the Arrhenius model fluctuated greatly (ranging from ±0.46 to ±38.29%) and most of it exceeded 10%. RBFNN model had the best predictive performance by comparing the residual and relative errors of the three models. CONCLUSION: RBFNN is a promising method for predicting the freshness of salmon fillets stored at -2 to 10 °C in the cold chain. © 2021 Society of Chemical Industry.


Assuntos
Produtos Pesqueiros/análise , Armazenamento de Alimentos/métodos , Animais , Qualidade dos Alimentos , Salmão , Temperatura
20.
Transl Neurodegener ; 10(1): 6, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33517891

RESUMO

As the most common form of dementia, Alzheimer's disease (AD) is characterized by progressive cognitive impairments and constitutes a major social burden. Currently, the invasiveness and high costs of tests have limited the early detection and intervention of the disease. As a unique window of the brain, retinal changes can reflect the pathology of the brain. In this review, we summarize current understanding of retinal structures in AD, mild cognitive impairment (MCI) and preclinical AD, focusing on neurodegeneration and microvascular changes measured using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) technologies. The literature suggests that the impairment of retinal microvascular network and neural microstructure exists in AD, MCI and even preclinical AD. These findings provide valuable insights into a better understanding of disease pathogenesis and demonstrate that retinal changes are potential biomarkers for early diagnosis of AD and monitoring of disease progression.

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