A novel role of AURKA kinase in erythroblast enucleation.

Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.

Metal-organic-framework derived NiS2/C hollow structures for enhanced polysulfide redox kinetics in lithium-sulfur batteries.

To cope with the shuttling of soluble lithium polysulfides in lithium-sulfur batteries, confinement tactics, such as trapping of sulfur within porous carbon structures, have been extensively studied. Although performance has improved a bit, the slow polysulfide conversion inducing fast capacity decay remains a big challenge. Herein, a NiS2/carbon (NiS2/C) composite with NiS2 nanoparticles embedded in a thin layer of carbon over the surface of micro-sized hollow structures has been prepared from Ni-metal-organic frameworks. These unique structures can physically entrap sulfur species and also influence their redox conversion kinetics. By improving the reaction kinetics of polysulfides, the NiS2/carbon@sulfur (NiS2/C@S) composite cathode with a suppressed shuttle effect shows a high columbic efficiency and decent rate performance. An initial capacity of 900 mAh g-1 at the rate of 1 C (1 C = 1675 mA g-1) and a low-capacity decline rate of 0.132% per cycle after 500 cycles are obtained, suggesting that this work provides a rational design of a sulfur cathode.

Diffuse optical tomography spatial prior for EEG source localization in human visual cortex.

Electroencephalography (EEG) and diffuse optical tomography (DOT) are imaging methods which are widely used for neuroimaging. While the temporal resolution of EEG is high, the spatial resolution is typically limited. DOT, on the other hand, has high spatial resolution, but the temporal resolution is inherently limited by the slow hemodynamics it measures. In our previous work, we showed using computer simulations that when using the results of DOT reconstruction as the spatial prior for EEG source reconstruction, high spatio-temporal resolution could be achieved. In this work, we experimentally validate the algorithm by alternatingly flashing two visual stimuli at a speed that is faster than the temporal resolution of DOT. We show that the joint reconstruction using both EEG and DOT clearly resolves the two stimuli temporally, and the spatial confinement is drastically improved in comparison to reconstruction using EEG alone.

A model of neurovascular coupling and its application to cortical spreading depolarization.

Cortical spreading depolarization (CSD) is a neuropathological condition involving propagating waves of neuronal silence, and is related to multiple diseases, such as migraine aura, traumatic brain injury (TBI), stroke, and cardiac arrest, as well as poor outcome of patients. While CSDs of different severity share similar roots on the ion exchange level, they can lead to different vascular responses (namely spreading hyperemia and spreading ischemia). In this paper, we propose a mathematical model relating neuronal activities to predict vascular changes as measured with near-infrared spectroscopy (NIRS) and fMRI recordings, and apply it to the extreme case of CSD, where sustained near-complete neuronal depolarization is seen. We utilize three serially connected models (namely, ion exchange, neurovascular coupling, and hemodynamic model) which are described by differential equations. Propagating waves of ion concentrations, as well as the associated vasodynamics and hemodynamics, are simulated by solving these equations. Our proposed model predicts vasodynamics and hemodynamics that agree both qualitatively and quantitatively with experimental literature. Mathematical modeling and simulation offer a powerful tool to help understand the underlying mechanisms of CSD and help interpret the data. In addition, it helps develop novel monitoring techniques prior to data collection. Our simulated results strongly suggest that fMRI is unable to reliably distinguish between spreading hyperemia and spreading ischemia, while NIRS signals are substantially distinct in the two cases.

The Development and Synthesis of a CdZnS @Metal-Organic Framework ZIF-8 for the Highly Efficient Photocatalytic Degradation of Organic Dyes.

The development of photocatalysts for organic degradation is a hot research topic. In this study, CdZnS was selected as the carrier, and ZIF-8 was combined with it to explore the photocatalytic performance of the composite. In addition, the compound material, CdZnS@ZIF-8, was used as a photocatalyst for the decomposition of methylene blue dye, and the performance of pure CdZnS and pure ZIF-8 was compared. The photocatalytic efficiency of CdZnS@ZIF-8 was significantly higher than that of the other two. In the experimental reaction, the amount of catalyst was 0.04 g, the pH value was 7, the initial concentration of methylene blue aqueous solution was 20 mg/L, and the degradation of methylene blue in 50 mL aqueous solution could reach 99.5% under visible light irradiation for 90 min, showing excellent photocatalytic efficiency in the visible light range. It demonstrated excellent photocatalytic function in the visible light region, and the electron transfer phenomenon at the interface occurred in the het-junction and the separation of the photo-generating electron-hole as an electron acceptor of ZIF-8 further promoted the photocatalytic effect.

Antibody development and property analysis of RhBST2 for accurate cell biological and viral research.

BST2 is a single-pass type II transmembrane (TM) protein, which has a cytoplasmic domain, a transmembrane domain, and an extracellular domain, each domain is important for biologic function of BST2. BST2 is a host restriction factor that can effectively inhibit retrovirus release. Rhesus monkeys are considered as relevant natural animal models for studying AIDS in humans. In order to recognize rhesus BST2 (RhBST2) protein and detect its function accurately, we prepared a polyclonal antibody (pAb) especially for RhBST2. Meanwhile, we constructed RhBST2 proteins with the addition of an HA-tag at the N-terminus (RhBST2-NHA) or inside of the ectodomain (RhBST2-IHA) to compare the recognition ability of rabbit anti-RhBST2 pAb and anti-HA mAb. The results showed that the anti-HA mAb and rabbit anti-RhBST2 pAb had the same ability to identify RhBST2. RhBST2 demonstrated antiviral activity and the ability to activate NF-κB. Moreover, the N-glycosylation states, cell surface level and intracellular localization of RhBST2 were detected. However, HA tags relatively changed part of the biological function of RhBST2. These results show that the RhBST2 polyclonal antibody is more suitable for analyzing the properties and functions of RhBST2, and the natural domain of RhBST2 is very important for its function.

Compensation of Rotary Encoders Using Fourier Expansion-Back Propagation Neural Network Optimized by Genetic Algorithm.

The measurement accuracy of the precision instruments that contain rotation joints is influenced significantly by the rotary encoders that are installed in the rotation joints. Apart from the imperfect manufacturing and installation of the rotary encoder, the variations of ambient temperature could cause the angle measurement error of the rotary encoder. According to the characteristics of the 2π periodicity of the angle measurement at the stationary temperature and the complexity of the effects of ambient temperature changes, the method based on the Fourier expansion-back propagation (BP) neural network optimized by genetic algorithm (FE-GABPNN) is proposed to improve the angle measurement accuracy of the rotary encoder. The proposed method, which innovatively integrates the characteristics of Fourier expansion, the BP neural network and genetic algorithm, has good fitting performance. The rotary encoder that is installed in the rotation joint of the articulated coordinate measuring machine (ACMM) is calibrated by using an autocollimator and a regular optical polygon at ambient temperature ranging from 10 to 40 °C. The contrastive analysis is carried out. The experimental results show that the angle measurement errors decrease remarkably, from 110.2″ to 2.7″ after compensation. The mean root mean square error (RMSE) of the residual errors is 0.85″.

Efficacy and Safety of Low-Dose Tirofiban for Acute Intracranial Atherosclerotic Stenosis Related Occlusion with Residual Stenosis after Endovascular Treatment.

BACKGROUND: The optimal treatment strategy for residual stenosis in patients with acute intracranial atherosclerotic stenosis related occlusion (ICAS-O) after endovascular treatment (EVT) is unknown. This study aims to evaluate the efficacy and safety of low-dose tirofiban in patients with residual stenosis after EVT due to acute ICAS-O. METHODS: Retrospective analysis of prospectively enrolled consecutive patients with residual stenosis after EVT due to acute ICAS-O from March 2015 to May 2019. Patients were divided into EVT alone group or EVT plus tirofiban group. The primary endpoint was the favorable functional outcome (defined as modified Rankin scale score of 0-2) at 90 days. The secondary endpoints were the proportions of reocclusion of recanalized arteries within 72 hours after EVT, symptomatic intracranial hemorrhage (sICH), any ICH, and mortality at 90 days. Logistic regression for predictors of reocclusion and functional outcomes were performed. RESULTS: A total of 98 patients, 50 treated with tirofiban and 48 without tirofiban, were enrolled in this study. Compared with patients in EVT alone group, patients in EVT plus tirofiban group had higher favorable functional outcome rate, lower mortality, and a lower reocclusion rate (56.3% versus 30.4%; P = .014, 8.3% versus 28.3%; P = .016, and 10.4% versus 32.6%; P = .011, respectively). The rates of any ICH and sICH were similar between the 2 groups. The use of tirofiban was associated with the favorable functional outcome (odds ratio [OR], 3.417; 95% confidence interval [CI], 1.149-10.163; P = .027) and lower reocclusion rate (OR, 0.145; 95% CI, 0.038-0.546; P = .004) on multivariate logistic regression analysis. CONCLUSIONS: In patients with residual stenosis after EVT due to acute ICAS-O, a low-dose of tirofiban is associated with favorable functional outcome and reduced incidence of reocclusion without increasing any ICH and sICH.

Temporal Dynamics of Shape Processing Differentiate Contributions of Dorsal and Ventral Visual Pathways.

Although shape perception is primarily considered a function of the ventral visual pathway, previous research has shown that both dorsal and ventral pathways represent shape information. Here, we examine whether the shape-selective electrophysiological signals observed in dorsal cortex are a product of the connectivity to ventral cortex or are independently computed. We conducted multiple EEG studies in which we manipulated the input parameters of the stimuli so as to bias processing to either the dorsal or ventral visual pathway. Participants viewed displays of common objects with shape information parametrically degraded across five levels. We measured shape sensitivity by regressing the amplitude of the evoked signal against the degree of stimulus scrambling. Experiment 1, which included grayscale versions of the stimuli, served as a benchmark establishing the temporal pattern of shape processing during typical object perception. These stimuli evoked broad and sustained patterns of shape sensitivity beginning as early as 50 msec after stimulus onset. In Experiments 2 and 3, we calibrated the stimuli such that visual information was delivered primarily through parvocellular inputs, which mainly project to the ventral pathway, or through koniocellular inputs, which mainly project to the dorsal pathway. In the second and third experiments, shape sensitivity was observed, but in distinct spatio-temporal configurations from each other and from that elicited by grayscale inputs. Of particular interest, in the koniocellular condition, shape selectivity emerged earlier than in the parvocellular condition. These findings support the conclusion of distinct dorsal pathway computations of object shape, independent from the ventral pathway.

Determination of the cleavage site of enterovirus 71 VP0 and the effect of this cleavage on viral infectivity and assembly.

Hand, foot, and mouth disease (HFMD) is a major public health concern, especially among infants and young children. The primary pathogen of HFMD is enterovirus 71 (EV71), whose capsid assembly mechanism including capsid protein processing has been widely studied. However, some of its mechanisms remain unclear, such as the VP0 cleavage. This study aimed to identify the cleavage site of the EV71 VP0 capsid protein and to elucidate the effects of EV71 VP0 cleavage on viral infectivity and assembly. A mass spectrometry analysis indicated that the cleavage site of EV71 VP0 is located between residues Lys69 and Ser70. To analyze the importance of either residue to cleavage, we designed single mutations of Lys69, Ser70 and double mutations respectively and implemented these genomes to encapsulation. The results indicated that Ser70 is more important for VP0 cleavage and EV71 infectivity. In addition, exogenous expression of EV71 protease 2A and 3C was used to verify whether they play roles in VP0 cleavage. Analyses also showed that none of them participate in this process. This study provides novel insights into the mechanisms of EV71 capsid maturation, which may be a potential target to improve the productivity and immunogenicity of EV71 vaccines.

On-line dynamic detection in the column chromatography separation based on an optical fiber surface plasmon resonance sensor.

In this design, we introduced a surface plasmon resonance (SPR) fiber-sensing probe into a column chromatography (CC) system to realize on-line dynamic detection in sample separation. The refractive index of the gel around the probe would be adjusted dynamically by the concentration change of the sample during CC separation. To demonstrate the separation and on-line detection process, bovine serum albumin (BSA) and riboflavin-5-phosphate sodium (FMN-Na) are chosen as the analytes in a Sephadex gel filtration chromatography system. The results show that the apparent reversible shift of the SPR spectrum can characterize the separation process. Specifically, the separated BSA with an outflow time of 8 min can cause a resonance wavelength shift of 15.5 nm, and the FMN-Na with an outflow time of 26 min can cause a shift of 8.4 nm. This on-line dynamic detection of SPR spectra has great potential to save time and simplify the analysis process compared to the complex thin layer chromatography detection steps in traditional manual CC.

Vitamin D deficiency increases the risk of diabetic peripheral neuropathy in elderly type 2 diabetes mellitus patients by predominantly increasing large-fiber lesions.

AIMS: This study explores the link between Vitamin D deficiency (VDD) and diabetic peripheral neuropathy (DPN) in elderly type 2 diabetes mellitus (T2DM) patients. METHODS: Involving 257 elderly T2DM patients, the study utilized propensity score matching to balance age, sex, and diabetes duration. VDD was defined as serum 25-hydroxyvitamin D [25(OH)D] levels below 20 ng/ml. Large nerve fiber lesions were evaluated by electromyogram, while small nerve fiber lesions were assessed by measuring skin conductance. RESULTS: DPN patients had notably lower serum 25(OH)D levels than non-DPN patients [15.05 vs. 18.4 ng/ml, P = 0.018]. VDD was identified as an independent risk factor for DPN (odds ratio = 2.488, P = 0.008) in multivariate logistic regression analysis. Spearman's correlation showed negative correlations between serum 25(OH)D levels and specific nerve latencies, and positive correlations with specific nerve velocities and amplitudes. The VDD group exhibited longer median sensory nerve latencies and motor evoked potential latencies compared to the vitamin D-sufficient group. Further, VDD is associated with the prolongation of the median motor nerve latency (odds ratio = 1.362, P = 0.038). CONCLUSIONS: VDD is independently associated with a higher risk of DPN. VDD may promote the development of DPN by affecting large nerve fibers.

Novel Angiotensin-Converting Enzyme-Inhibitory Peptides Obtained from Trichiurus lepturus: Preparation, Identification and Potential Antihypertensive Mechanism.

Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation of Trichiurus lepturus (ribbonfish) using alkaline protease. The resulting mixture underwent filtration using centrifugation, ultrafiltration tubes, and Sephadex G-25 gels. Peptides exhibiting ACE-inhibitory properties and DPPH free-radical-scavenging abilities were isolated and subsequently purified via LC/MS-MS, leading to the identification of over 100 peptide components. In silico screening yielded five ACE inhibitory peptides: FAGDDAPR, QGPIGPR, IFPRNPP, AGFAGDDAPR, and GPTGPAGPR. Among these, IFPRNPP and AGFAGDDAPR were found to be allergenic, while FAGDDAPRR, QGPIGPR, and GPTGPAGP showed good ACE-inhibitory effects. IC50 values for the latter peptides were obtained from HUVEC cells: FAGDDAPRR (IC50 = 262.98 µM), QGPIGPR (IC50 = 81.09 µM), and GPTGPAGP (IC50 = 168.11 µM). Peptide constituents derived from ribbonfish proteins effectively modulated ACE activity, thus underscoring their therapeutic potential. Molecular docking and modeling corroborated these findings, emphasizing the utility of functional foods as a promising avenue for the treatment and prevention of hypertension, with potential ancillary health benefits and applications as substitutes for synthetic drugs.

Sema4D as a biomarker for Predicting rheumatoid arthritis disease activity.

OBJECTIVE: The semaphorins are membrane or secreted proteins first identified in neural development. Semaphorin 4D (Sema4D) is the first family member found to have immune properties. We evaluated the potential of Sema4D as a marker for rheumatoid arthritis (RA) disease activity, singly and in combination with other known biomarkers including rheumatoid factor (RF) and C-reactive protein (CRP). METHODS: Three hundred and eleven RA patients were enrolled. The patients were divided into three groups based on their disease activity in 28 joints (DAS28): mild, moderate, and severe. The healthy group included 40 healthy individuals. SerumSema4D was measured by quantitative ELISA and the specificity and sensitivity of biomarkers were evaluated by generating a receiver operating characteristic (ROC) curve to analyze their diagnostic accuracy. RESULTS: Serum Sema4D levels in the moderate and severe RA groups were elevated significantly above those of the controls (P < 0.01), while levels in the mild RA and control groups did not differ significantly (P > 0.05). The Sema4D cutoff threshold was 15.7 ng/ml when the DAS28 was applied as a reference. Compared to the erythrocyte sedimentation rate (ESR and CRP, Sema4D had the highest specificity (96.8%) and area under the curve (0.80) for diagnosing RA activity. The highest specificity (100%) for the biomarker combinations was obtained when Sema4D was combined with CRP and anti-CCP, the combination of the Sema4D combined with ESR and anti-CCP had the highest sensitivity (99.35%). According to this result, a new model for jointly calculating RA activity of Sema4D,anti-CCP and CRP was constructed. Meanwhile another model is established by using the method of multivariate analysis.Model comparison results showed the the multiple regression algorithm method fitted the patients' disease activity better. CONCLUSION: The serum Sema 4D level effectively reflects moderate to severe RA activity. Sema4D levels can be used together with conventional RA biomarkers to increase the diagnostic power of RA activity. The multiple regression algorithm method is promising in disease activity calculation.

A Stabilized Li-Metal Anode with a Ti-Based Metal-Organic Framework Electronic Shield.

The insufficient cyclic efficiency and poor safety have prohibited the commercial applications of the lithium-metal anode because of its uncontrolled dendrite growth at the surface. A mechanically stable and highly ionic conductive solid electrolyte interphase (SEI) holds great promise to address the issues. Herein, a viable surface engineering approach is proposed for stabilizing the Li anode via a scalable artificial method. The surface of Li metal is functionalized by constructing a mechanically tough and electron-insulating metal-organic framework (MOF) of the MIL-125(Ti) layer. In-situ optical microscopy reveals its crucial role in inhibiting dendritic Li growth. Because of the intrinsic insulativity and highly ordered micropores of MIL-125(Ti), the Li+ ions acquire electrons under the coating layer, resulting in a uniform and dense Li deposition behavior. The symmetric cell of the MOF-modified Li electrode delivers a long life span of 2000 h with an overpotential of less than 20 mV at 0.5 mA cm-2. When paired with the same MOF-derived sulfur cathode, decent cycling retention is available as well. This work demonstrates a feasible strategy for the development of a stable Li-metal anode with alleviative dendritic growth.

Scaling of Algorithmic Bias in Pulse Oximetry with Signal-to-Noise Ratio.

Recent work has noted a skin-color bias in existing pulse oximetry systems in their estimation of arterial oxygen saturation. Frequently, the algorithm used by these systems estimate a "ratio-of-ratios", called the "R-value", on their way to estimating the oxygen saturation. In this work, we focus on an "SNR-related" bias that is due to noise in measurements. We derive expressions for the SNR-related bias in R-value estimation, and observe how it scales with the signal-to-noise ratio (SNR). We show that the bias can arise at two steps of R-value estimation: in estimating the max and min of a pulsatile signal, and, additionally in taking ratios to estimate the R-value. We assess the bias resulting from the combination of the two steps, but also separate out contributions of each step. By doing so, we deduce that the bias induced in max and min estimation is likely to dominate. Because the SNR tends to get worse with higher melanin concentration, our result provides a sense of scaling of this bias with melanin concentration.

Prognostic value of an eighteen-genes panel in acute myeloid leukemia by analyzing TARGET and TCGA databases.

BACKGROUND: Acute myeloid leukemia (AML) has a poor prognosis, and the current 5-year survival rate is less than 30%. OBJECTIVE: The present study was designed to identify the significant genes closely related to AML prognosis and predict the prognostic value by constructing a risk model based on their expression. METHODS: Using bioinformatics (Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, univariate and multivariate Cox regression analysis, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) analysis) to identify a prognostic gene signature for AML. Finally, The Cancer Genome Atlas (TCGA) database was used to validate this prognostic signature. RESULTS: Based on univariate and multivariate Cox regression analysis, eighteen prognostic genes were identified, and the gene signature and risk score model were constructed. Multivariate Cox analysis showed that the risk score was an independent prognostic factor [hazard ratio (HR) = 1.122, 95% confidence interval (CI) = 1.067-1.180, P< 0.001]. ROC analysis showed a high predictive value of the risk model with an area under the curve (AUC) of 0.705. CONCLUSIONS: This study evaluated a potential prognostic signature with eighteen genes and constructed a risk model significantly related to the prognosis of AML patients.

Evaluating feasibility of functional near-infrared spectroscopy in dolphins.

Significance: Using functional near-infrared spectroscopy (fNIRS) in bottlenose dolphins (Tursiops truncatus) could help to understand how echolocating animals perceive their environment and how they focus on specific auditory objects, such as fish, in noisy marine settings. Aim: To test the feasibility of near-infrared spectroscopy (NIRS) in medium-sized marine mammals, such as dolphins, we modeled the light propagation with computational tools to determine the wavelengths, optode locations, and separation distances that maximize sensitivity to brain tissue. Approach: Using frequency-domain NIRS, we measured the absorption and reduced scattering coefficient of dolphin sculp. We assigned muscle, bone, and brain optical properties from the literature and modeled light propagation in a spatially accurate and biologically relevant model of a dolphin head, using finite-element modeling. We assessed tissue sensitivities for a range of wavelengths (600 to 1700 nm), source-detector distances (50 to 120 mm), and animal sizes (juvenile model 25% smaller than adult). Results: We found that the wavelengths most suitable for imaging the brain fell into two ranges: 700 to 900 nm and 1100 to 1150 nm. The optimal location for brain sensing positioned the center point between source and detector 30 to 50 mm caudal of the blowhole and at an angle 45 deg to 90 deg lateral off the midsagittal plane. Brain tissue sensitivity comparable to human measurements appears achievable only for smaller animals, such as juvenile bottlenose dolphins or smaller species of cetaceans, such as porpoises, or with source-detector separations ≫100 mm in adult dolphins. Conclusions: Brain measurements in juvenile or subadult dolphins, or smaller dolphin species, may be possible using specialized fNIRS devices that support optode separations of >100 mm. We speculate that many measurement repetitions will be required to overcome hemodynamic signals originating predominantly from the muscle layer above the skull. NIRS measurements of muscle tissue are feasible today with source-detector separations of 50 mm, or even less.

Comprehensive analysis of thirteen-gene panel with prognosis value in Multiple Myeloma.

BACKGROUND: Although there are many treatments for Multiple myeloma (MM), patients with MM still unable to escape the recurrence and aggravation of the disease. OBJECTIVE: We constructed a risk model based on genes closely associated with MM prognosis to predict its prognostic value. METHODS: Gene function enrichment and signal pathway enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, univariate and multivariate Cox regression analysis, Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) analysis were used to identify the prognostic gene signature for MM. Finally, the prognostic gene signature was validated using the Gene Expression Omnibus (GEO) database. RESULTS: Thirteen prognostic genes were screened by univariate Cox analysis and LASSO regression analysis. Multivariate Cox analysis revealed risk score to be an independent prognostic factor for patients with MM [Hazard Ratio (HR) = 2.564, 95% Confidence Interval (CI) = 2.223-2.958, P< 0.001]. The risk score had a high level of predictive value according to ROC analysis, with an area under the curve (AUC) of 0.744. CONCLUSIONS: The potential prognostic signature of thirteen genes were assessed and a risk model was constructed that significantly correlated with prognosis in MM patients.

Production of cyclic adenosine monophosphate by Arthrobacter sp. A302 using fed-batch fermentation with pH-shift control.

The production of cyclic adenosine monophosphate (cAMP) by Arthrobacter sp. A302 was studied in a 5 L stirred tank fermentor under a range of pH values (6.5-8.0) and glucose feeding rates. In batch fermentation under a controlled pH, the optimum pH for cell growth was 7.5 with dry cell density (X) of 11.43 g L, and the optimum pH for cAMP accumulation was 7.0 with cAMP concentration of 7.41 g L. In order to achieve the high X and cAMP yield simultaneously, a pH-shift control strategy was proposed based on kinetic analysis of specific cell growth rate (µ) and specific cAMP formation rate (q ( s )). In this method, pH was controlled to 7.0 for the first 30 h of fermentation, and then subsequently shifted to 7.5 and maintained until the end of the process. Application of this approach significantly enhanced the cAMP concentration. Thereafter, cAMP production was further improved by combining the above-mentioned pH-control system and fed-batch process with glucose at a constant feeding rate of 1.0 g L(-1 )h(-1). Under optimum conditions, the final cAMP production was 10.87 g L, which is 110.0, 46.7, and 27.7% higher than that of the pH-uncontrolled, pH-controlled, and pH-shift controlled methods, respectively.