A domain-general frontoparietal network interacts with domain-preferential intermediate pathways to support working memory task.

Working memory (WM) is essential for cognition, but the underlying neural mechanisms remain elusive. From a hierarchical processing perspective, this paper proposed and tested a hypothesis that a domain-general network at the top of the WM hierarchy can interact with distinct domain-preferential intermediate circuits to support WM. Employing a novel N-back task, we first identified the posterior superior temporal gyrus (pSTG), middle temporal area (MT), and postcentral gyrus (PoCG) as intermediate regions for biological motion and shape motion processing, respectively. Using further psychophysiological interaction analyses, we delineated a frontal-parietal network (FPN) as the domain-general network. These results were further verified and extended by a delayed match to sample (DMS) task. Although the WM load-dependent and stimulus-free activations during the DMS delay phase confirm the role of FPN as a domain-general network to maintain information, the stimulus-dependent activations within this network during the DMS encoding phase suggest its involvement in the final stage of the hierarchical processing chains. In contrast, the load-dependent activations of intermediate regions in the N-back task highlight their further roles beyond perception in WM tasks. These results provide empirical evidence for a hierarchical processing model of WM and may have significant implications for WM training.

Association Between Endothelial Activation and Stress Index and 28-Day Mortality in Septic ICU patients: a Retrospective Cohort Study.

Background: Endothelial Activation and Stress Index (EASIX) is a reliable alternative biomarker of endothelial dysfunction. Because endothelial activation is involved in sepsis pathophysiology, we aimed to investigate the association between EASIX and prognosis in septic patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV database. EASIX scores were calculated using the formula: lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelet count (109/L). Patients were grouped into tertiles according to log2 transformed EASIX. The primary and secondary outcomes were 28-day and 90-day mortality. Cox proportional hazards models, Kaplan-Meier curves, restricted cubic spline curves, and subgroup analyses were conducted to evaluate the association between EASIX and prognosis in septic patients. Results: A total of 7504 patients were included. Multivariable Cox proportional hazards analyses showed that higher log2-EASIX was associated with increased risk of 28-day mortality (HR, 1.10; 95% CI, 1.07-1.13; P < 0.001). Compared with tertile 1, the tertile 2 and 3 groups had higher risk of 28-day mortality [HR (95% CI) 1.24 (1.09-1.41); HR (95% CI) 1.51 (1.31-1.74)]; P for trend < 0.001). Similar results were found for 90-day mortality. Kaplan-Meier curves showed that patients with higher EASIX had lower 28-day and 90-day survival rates. A linear relationship was found between log2-EASIX and 28-day and 90-day mortality. Conclusion: High EASIX was significantly associated with an increased risk of 28-day and 90-day all-cause mortality in patients with sepsis.

Uptake of HIV testing and its correlates among sexually experienced college students in Southwestern, China: a Web-Based online cross-sectional study.

BACKGROUND: The prevalence of human immunodeficiency virus (HIV) is becoming more common among college students in China. However, latest data on the prevalence and correlates of HIV testing among sexually experienced college students is rarely. METHODS: An online survey was conducted among college students aged 18 years or older using multistage stratified cluster sampling from 16 colleges. Data on socio-demographic, HIV testing, HIV-related awareness, attitudes, sexual education and behaviors were collected. Propensity score matching (PSM) and logistic regression model were used to identify factors associated with HIV testing. RESULT: A total of 108,987 students participated the survey, of which 13,201 sexually experienced college students were included in this study. 1,939 (14.69%) college students with sexual experience reported uptake of HIV testing in the preceding year. The uptake of HIV testing increased for college students with a rising HIV knowledge score and sexual health knowledge. Being awareness of HIV-related knowledge (aOR = 1.15, 95%CI: 1.01-1.30), accepting one-night stands (aOR = 1.16, 95%CI:1.03-1.32), obtaining satisfactory sexual interpretation from parent(s) (aOR = 1.24, 95%CI: 1.07-1.43), ever had unintended pregnancy (aOR = 1.78, 95%CI: 1.32-2.38), ever had received HIV-related preventive service(s) (aOR = 1.37, 95%CI: 1.10-1.70), ever had participated HIV-related preventive services (aOR = 3.76, 95%CI: 2.99-4.75) and ever had anal sex (aOR = 2.66, 95%CI: 2.11-3.34) were positively associated with uptake of HIV testing. However, accepting premarital sex (aOR = 0.76, 95%CI: 0.66-0.88), accepting cohabitation (aOR = 0.75, 95%CI: 0.61-0.92), occasionally discussing sex with parent(s) (aOR = 0.68, 95%CI: 0.50-0.91), and being with moderate satisfaction of school sex courses (aOR = 0.74, 95%CI: 0.58-0.95) were negatively associated with uptake of HIV testing. CONCLUSION: The prevalence of HIV testing was relatively low. Participation in HIV-related services and high-risk sexual behaviors were important enablers for testing. Improving sex education for students, increasing HIV preventive services on campus, and improving family sex education are necessary to increase HIV testing among college sexually experienced students.

Reversible Adsorption and Detachment of Saccharomyces cerevisiae on Thermoresponsive Poly(N-isopropylacrylamide)-Grafted Fibers for Continuous Immobilized Fermentation.

Biofilm-mediated continuous fermentation with cells immobilized has gained much attention in recent years. In this study, thermoresponsive poly(N-isopropylacrylamide)-grafted cotton fibers (PNIPAM-CF) were prepared via an improved surface-initiated atom transfer radical polymerization. The modification process imparted switchable wettability to the surface while maintaining the thermal stability and biocompatibility of the CF. During the ethanol transformation, the rapid, reversible cell adsorption and detachment of Saccharomyces cerevisiae were performed through the modulation of wettability, displaying the enhancement of immobilized biomass and immobilization efficiency from 2.20 g/L and 59.43% to 2.81 g/L and 93.32%, respectively. Moreover, the biofilm adsorption matched well with the Freundlich model, indicating that multilayer adhesion was the main mode of biofilm formation. Based on the accumulation of the biofilm, the fabrication and utilization of PNIPAM-CF improved the efficiency of continuous immobilized fermentation, making the ethanol production reach 26.34 g/L in the sixth batch of fermentation. Meanwhile, wettability regulation further enhanced the reusability of the carrier. Therefore, the findings of this study revealed that the application of smart materials in cell immobilization systems had broad prospects for achieving sustainable and continuous catalysis.

Impact of Left Atrial Appendage Closure Combined with Catheter Ablation on Endocrine and Mechanical Cardiac Function in Patients with Atrial Fibrillation.

Background: The combined procedure of left atrial appendage closure (LAAC) and catheter ablation (CA) is a safe and feasible therapy to treat patients with atrial fibrillation (AF). However, the effect of the combined procedure on cardiac function remains unclear. This study aimed to investigate the changes in endocrine and mechanical function of the heart following the combined procedure. Methods: This retrospective study included 62 consecutive patients who underwent the combined procedure of AF ablation and WATCHMAN LAAC and 62 sex and age-matched patients who only received AF ablation. During follow-up, patients were examined for brain natriuretic peptide (BNP) levels to represent endocrine cardiac function. Mechanical cardiac function was assessed during echocardiographic examination by means of the LA ejection fraction, LA strain (Ƹ), and LA strain rate (SR). Results: (1) The BNP levels decreased acutely after the procedure, rose at day 3 postoperation, but trended downwards at 3 months postoperation in both groups. No significant difference was observed between the two groups. (2) LA ejection fraction, LA Ƹ, and SR exhibited a continuous upward trend over a 3-month follow-up in both groups. There was no significant difference in LA ejection fractions, SRe (the parameter of LA conduit function), and SRa (the parameter of LA booster pump function) between the two groups. However, the Ƹ and SRs (the parameters of LA reservoir function) improved in patients treated with CA alone. Conclusions: The combined procedure of LAAC and CA significantly improved the endocrine and mechanical function of the heart. Compared to simple CA, based on CA with LAAC intervention, it does not significantly change LA endocrine function but may lead to a decline in the LA reservoir function.

Synthesis and evaluation of inhibitors of Mycobacterium tuberculosis UGM using bioisosteric replacement.

There is a dearth of tuberculosis (TB) drug development activity as current therapeutic treatments are inadequate due to the appearance of drug-resistant TB. The enzyme UDP-galactopyranose mutase (UGM) is involved in the biosynthesis of galactan which is essential for cell wall integrity and bacterial viability. Its inhibition has thus been featured as profitable strategy for anti-TB drug discovery. In this study, we report on the synthesis of amides derived from rosmarinic acid, their inhibitory effect towards purified UGM using three distinct biochemical assays: FP, HPLC and SPR. The rosmarinic amides generally showed a significantly higher affinity for UGM than the corresponding rosmarinic ester. In particular, compound 5h displayed interesting binding affinity values (Kd = 58 ± 7, 63 ± 9 µM towards KpUGM and MtUGM respectively). Furthermore, a new UGM SPR assay was established and confirmed that 5h binds to UGM with a dissociation constant of 104.8 ± 6.5 µM. Collectively, this study validates the amide bioisosteric strategy which has been successfully implemented to develop UGM inhibitors from rosmarinic acid, providing a substantial basis for further design of novel UGM inhibitors and anti-mycobacterial agents.

The effect of different preoperative left atrial appendage emptying speeds on left atrial function in patients with persistent atrial fibrillation after left atrial appendage closure combined with catheter ablation.

OBJECTIVE: The present study aimed to investigate whether different preoperative left atrial appendage emptying speeds (LAAEVs) have an effect on left atrial function in patients with sinus arrhythmia after left atrial appendage closure (LAAC) combined with catheter ablation (CA). METHODS: A total of 163 patients with persistent non-valvular atrial fibrillation who received combined LAAC+CA surgery were included in the present study. Regular follow-up was conducted for 12 months, and patients with complete data and successful sinus rhythm recovery were selected as the study subjects (n = 82). The patients were divided into two groups: the LAAEV < 25 cm/s group and the LAAEV ≥ 25 cm/s group (n = 41 each). The propensity score was used for matching according to gender, age, CHA2DS2-VASc score, and HAS-BLED score. The changes in the two groups in LA structure, storage function, conduit function, and pump function were compared. RESULTS: Before surgery, the maximum LA volume (LAVmax) and minimum LA volume (LAVmin) were greater in the LAAEV < 25 cm/s group than in the LAAEV ≥ 25 cm/s group. The LA storage function (eg. Ƹ and SRs), conduit function (eg. SRe), and pump function (eg. SRa) were all worse in the LAAEV < 25 cm/s group than in the LAAEV ≥ 25 cm/s group. After the combined LAAC+CA surgery, the LA storage, conduit, and pump functions improved in both groups. At 12 months after surgery, there were no statistically significant differences between the two groups. CONCLUSION: Before combined LAAC+CA surgery, the LA structure and function of the LAAEV < 25 cm/s group were worse than those of the LAAEV ≥ 25 cm/s group. However, after LAAC+CA surgery, the LA structure and function of the patients were improved, and there were no significant differences between the two groups. Inferred improvement in LA structure and function in the LAAEV < 25 cm/s group was superior to that in the LAAEV ≥ 25 cm/s group.

The institutional primary healthcare service quality and patients' experiences in Chinese community health centres: results from the Greater Bay Area study, China.

BACKGROUND: The goal of this paper was to assess the quality of primary healthcare services at community health centres (CHCs) from the demand (patient) and supplier (healthcare service institution) angles. METHODS: This study was conducted at six CHCs in the Greater Bay Area of China. Between August and October 2019, 1,568 patients were recruited (55.8% women and 44.2% men). We evaluated the service quality of CHCs using the National Committee for Quality Assurance Patient-Centred Medical Home (NCQA-PCMH) recognition questionnaire. We assessed patients' experiences with medical and health services using the Primary Care Assessment Tools (PCAT). RESULTS: PCAT total and sub-domains scores were significantly difference at the six CHCs (P < 0.001). Among the six CHCs, Shayuan CHC had the highest PCAT total and sub-domain scores and the highest NCQA-PCMH total and sub-domain scores, as well. Older (> 60 years), female, lower education, and employee medical-insured individuals had better patient experiences. CONCLUSIONS: Our results indicate that CHCs could improve their service quality by improving both institutional health service quality based on NCQA-PCMH assessment and patient experiences based on PCAT scales. These findings can help inform patient-centred primary healthcare policy and management.

Inflammatory Response after Different Ablation Strategies for Paroxysmal Atrial Fibrillation.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) has been gaining popularity; however, the trend of inflammatory response markers in patients treated with different catheter ablation strategies over time and their predictability of AF recurrence remain unknown. METHODS: A total of 210 patients with AF were enrolled and grouped according to surgical mode as follows: freeze group, RF group, and freeze3D group. The subjects were tested for related indexes before and after surgery. To determine AF recurrence during follow up, 24-h ambulatory electrocardiography was performed at two, three, six, and 12 months after surgery. RESULTS: The inflammation indexes of the three groups peaked between one and three days after surgery but fell at different time points (P < .05). The recurrence rate of paroxysmal atrial fibrillation (PAF) was positively correlated with the increase in the percentage of white blood cells and neutrophils after surgery (P < .05). CONCLUSIONS: The postoperative inflammation indices peaked and fell at different time points after different catheter ablation methods. In addition, the recurrence rate of AF in patients treated with freeze3D is lower.

Influence of urban green open space on residents' physical activity in China.

BACKGROUND: Urban green open space is a valuable resource for physical activities of urban inhabitants and has the potential to reduce chronic illness and improve health. Research on the relationships between green open space and physical activity is incomplete and limited in China. Thus, the study examines how the urban green open space contributes to physical activity. METHODS: A questionnaire was designed based on the social ecology theory to investigate the physical activity of 513 residents in urban green open space. We use the time and frequency of residents exercising in urban green space to measure physical activity, and use the factor analysis to synthesize a large number of original factors (i.e., infrastructure, safety, accessibility, landscape quality, and space environment) into relatively few composite indicators. Based on the collected data of the cross-sectional population, the Order Probit regression model was constructed to analyze how urban green open space affects the residents' physical activity from the perspective of social ecology. RESULTS: ① in community factors: accessibility is significantly positive correlation with residents' physical activity, and there is no significant correlation between safety and physical activity; ②in natural factors: space environment and landscape quality are not significantly correlated with residents' physical activity; ③ in built environmental factors: infrastructures, the area of green space, the size of open space, and entertainment facilities are significantly correlated to residents' activity. Basketball courts, volleyball courts, swimming pools, and sports equipment will promote physical activity; ④ apart from the attributes of green open space, other factors are significantly correlated to physical activity in the green open space, e.g. having a companion. CONCLUSIONS: Urban green open space plays an important role in promoting physical activity especially among the women and the old, and improving the attributes (such as accessibility, infrastructures, the area of green space, the size of open space and entertainment facilities) of the urban green open space and trying to set up group sports proper to play with companion (like "square dancing" and "Tai Chi") can promote Chinese residents' physical activity so as to improve public health. The results are significant to facilitate environment health.

Competitive adsorption of vanillin and syringaldehyde on a macro-mesopore polymeric resin: modeling.

Vanillin and syringaldehyde are widely used as flavoring and fragrance agents in the food products. The potential of a macro-mesoporous adsorption resin was assessed for separation of these binary mixtures. This work focuses on modeling of the competitive adsorption behaviors and exploration of the adsorption mechanism. The characterization results showed the resin had a large BET surface area and specific pore structure with hydrophobic properties. By analysis of the physicochemical properties of the solutes and the resin, the separation mechanism was mainly contributed by hydrophobic effect. Subsequently, the competitive Langmuir isotherm model was used to fit the competitive adsorption isotherms. The pore diffusion coefficient was obtained by macropore diffusion model. Afterwards, a mathematical model was established to predict the breakthrough curves of the binary mixture at various operating conditions. The data and model presented are valuable for design and simulation of the continuous chromatographic separation process.

Towards acetone-uncoupled biofuels production in solventogenic Clostridium through reducing power conservation.

Microbial production of butanol by solventogenic Clostridium has long been complicated with the formation of acetone as an unwanted product, which causes poor product yields and creates a most important problem concerning substrate transformation. Intensive attempts concentrate on carbon conversion pathways to eliminate acetone, but have actually achieved little so far. Here, we believe microbial product distribution can largely depend on how the cell plays its energetic cofactors in central metabolism, and demonstrate that by introducing a synthetic 2,3-butanediol synthesis pathway in Clostridium acetobutylicum as an NADH-compensating module to readjust the reducing power at a systems level, the production of acetone can be selectively and efficiently eliminated (< 0.3 g/L). H2 evolution was reduced by 78%, and the total alcohol yield was strikingly increased by 19% to 0.44 g/g glucose, much higher than those yet reported for butanol fermentation. These findings highlight that it is the loss of reducing power rather than typically manipulated solventogenesis genes that dominates acetone formation. Further study revealed that the NADH-module triggered apparent regulation of pathways involved in electron transfer and reducing power conservation. The study also suggested the key to conservation of intracellular reducing power might essentially lie in the intermediate processes in central metabolism that are related to redox partners, butyrate or C4 branches, and possibly NADH and NADPH specificity. This study represents the first effective redox-based configuration of C. acetobutylicum and provides valuable understandings for redox engineering of native Clostridium species towards advanced production of biofuels and alcohols.

Early Seizure Prophylaxis in Traumatic Brain Injuries Revisited: A Prospective Observational Study.

INTRODUCTION: Pharmacological prophylaxis for early seizures following traumatic brain injury (TBI) is a recommendation in the Brain Trauma Foundation Guidelines. However, several studies have challenged the efficacy and safety of this practice, resulting in varied practice across centers around the world. The purpose of the present study was to compare the incidence of early clinical seizures following TBI, between two large centers, a US Center that practises routine seizure prophylaxis and a Chinese Center that does not use seizure prophylaxis following TBI. PATIENTS AND METHODS: This was a prospective observational study including an urban level I trauma center in the USA and a large hospital in Shenzhen, China. At the US Center, all patients received seizure prophylaxis with levetiracetam. At the Chinese Center, no seizure prophylaxis was given. All patients with blunt TBI and positive computed tomography findings for epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intracerebral hemorrhage or diffuse axonal injury were included. Patients who died within 24 h of admission were excluded. The study population was monitored daily for clinical seizures for the first 7 post-injury days. Data collected included demographics, mechanism of injury, vital signs upon arrival, injury severity and emergency interventions. Primary outcome was the incidence of early seizures, defined as those occurring within 7 days of injury. RESULTS: A total of 522 patients were included in the analysis: 272 patients at the US Center who received seizure prophylaxis and 250 patients at the Chinese Center who did not receive prophylaxis. Overall, 3.7% of patients who received seizure prophylaxis developed early seizures, compared to 2.8% of patients who did not receive any prophylaxis (p = 0.573). Decompressive craniectomy was associated with the highest incidence of early seizure (9.2%). In this subgroup, the seizure rate was 10.4% in the prophylaxis group and 7.1% in the no-prophylaxis group (p = 0.738). Patients with admission GCS < 9 had an overall early seizure incidence of 7.0%: 4.3% in the prophylaxis group and 14.3% in the no-prophylaxis group (p = 0.062). Analysis of the subgroup with isolated blunt TBI showed an incidence of early seizures of 3.4% in the prophylaxis group versus 2.4% in the no-prophylaxis group (p = 0.593). Further analyses of outcomes according to head AIS 3, 4 and 5 showed no significant difference in the seizure rate between the two groups: head AIS 3: 6.1% in the prophylaxis group versus 2.6% in the no-prophylaxis group, p = 0.329; head AIS 4: 0 versus 2.7%, p = 0.302; head AIS 5: 8.7 versus 4.0%, p = 0.601. CONCLUSIONS: The present study failed to show any benefit of routine early seizure prophylaxis following blunt TBI. This practice should be reexamined in a large randomized clinical study.

Decreased Serum Brain-Derived Neurotrophic Factor May Indicate the Development of Poststroke Depression in Patients with Acute Ischemic Stroke: A Meta-Analysis.

BACKGROUND: Depression is a common complication after stroke and has been associated with poor outcome. Thus, it is of great importance to identify potential biomarkers that can aid in predicting and detecting patients with stroke at high risk of poststroke depression (PSD) development. Previous studies showed that brain-derived neurotrophic factor (BDNF) had potential use as a biomarker for discriminating patients with stroke at high risk of PSD. However, the results were inconsistent. METHODS: A meta-analysis was performed to evaluate the correlation between the peripheral BDNF levels and the development of PSD in the acute stage of stroke. RESULTS: Data were obtained from 4 studies including 499 patients with stroke. Among them, 171 patients were diagnosed with PSD at follow-ups. Our results showed that patients with stroke who were predisposed to developing PSD had significantly lower serum BDNF concentrations at the early stage of stroke. CONCLUSIONS: This study suggests a potential association between circulating BDNF concentrations at admission and subsequent PSD development, and provides additional support for the involvement of BDNF in the PSD development.

Efficient immobilization of AGE and NAL enzymes onto functional amino resin as recyclable and high-performance biocatalyst.

N-Acetylglucosamine-2-epimerase (AGE) and N-acetylneuraminic acid lyase (NAL) were immobilized for synthesis of N-acetylneuraminic acid (Neu5Ac) on three resins: Amberzyme oxirane resin (AOR), poly (styrene-co-DVB)-Br resin (PBR) and amino resin (AR). The loading capacity and immobilized enzyme activity showed that AR was the best carrier. Three methods of glutaraldehyde cross-linking were tested and simultaneous cross-linking and immobilization was demonstrated to be the best method. The functional properties of immobilized AGE and NAL were studied and compared to those of the free enzyme. The highest enzyme activities of free and immobilized AGE were obtained in 0.1 M potassium phosphate buffer at pH 7.5 and a temperature of 37 °C. Comparatively, the highest NAL activities were at pH 8.5. Meanwhile, an increase in K m (from 1.14 to 1.31 mg·mL-1 for AGE and from 1.05 to 1.25 mg·mL-1 for NAL) and a decrease in V max (from 177.53 to 106.37 µg·min-1 mL-1 for AGE and from 126.41 to 95.96 µg·min-1 mL-1 for NAL) were recorded after immobilization. The AR-glutaraldehyde-enzyme system exhibited better thermal stability than the free enzyme, and retained 72% of its initial activity even after eight repeated runs. The apparent activation energy (E a) of the free and immobilized AGE (NAL) was 117.14 kJ·mol-1 (124.21 kJ·mol-1) and 78.45 kJ·mol-1 (66.64 kJ·mol-1), respectively, implying that the catalytic efficiency of the immobilized enzyme was restricted by mass-transfer rather than kinetic limit. Subsequently, Neu5Ac production from GlcNAc using immobilized enzymes in one reactor was carried out resulting 101.45 g·L-1 of Neu5Ac and the highest conversion ratio of 82%. This method of enzyme immobilization may have a promising future for Neu5Ac production in industry.

Screening of promoters from Arthrobacter sp. CGMCC 3584 using a green fluorescent protein reporter system.

Available molecular and genetic tools for the genetic manipulation of Arthrobacter species are limited until now. In gene engineering, a continuous set of promoters with various strengths are of importance for fine-tuning gene expression in metabolic optimization and control analysis. Here, for the first time, we constructed a promoter trap system using green fluorescence protein (GFP) as a reporter, for screening and characterizing functional Arthrobacter promoters. Twenty-three Arthrobacter transformants of various GFP fluorescence strengths were isolated and characterized through the analysis of DNA sequences. Among the 23 putative promoters, 2 were selected for deletion analysis of promoter elements. As a result, the deletion of the upstream of the putative promoter P8 and P13 caused a 43.8% decrease and a 29.1% increase in the fluorescence signals, respectively. Finally, we obtained the strongest promoter P13-3 which was 4.4 times more potent than the promoter of 6-hydroxyl-D-nicotine oxidase gene which was previously reported in Arthrobacter nicotinovorans, and the obtained promoter was used to improve the production of cyclic adenosine monophosphate in Arthrobacter sp. CGMCC 3584. The screening strategy together with obtained promoters in this study would contribute to the future engineering of Arthrobacter species.

[Design of ECG Signal Acquisition Terminal Based on ADS1298R].

The home health monitoring of the ECG signal acquisition and display terminal is designed with MSP430F6659 and ADS1298R chip of TI company. The basic principles of ECG col ection is introduced in the beginning, and then the overal scheme of the system is described by MSP430F6659 and ADS1298R chip as the core, and the modules peripheral interface, real-time display in LCD, data storage and USB are introduced. The ECG signal acquisition terminal designed in this paper has the characteristics of smal size, low power consumption and so on.

Redirecting metabolic flux in Saccharomyces cerevisiae through regulation of cofactors in UMP production.

Although it is generally known that cofactors play a major role in the production of different fermentation products, their role has not been thoroughly and systematically studied. To understand the impact of cofactors on physiological functions, a systematic approach was applied, which involved redox state analysis, energy charge analysis, and metabolite analysis. Using uridine 5'-monophosphate metabolism in Saccharomyces cerevisiae as a model, we demonstrated that regulation of intracellular the ratio of NADPH to NADP(+) not only redistributed the carbon flux between the glycolytic and pentose phosphate pathways, but also regulated the redox state of NAD(H), resulting in a significant change of ATP, and a significantly altered spectrum of metabolic products.

A novel procedure for purification of uridine 5'-monophosphate based on adsorption methodology using a hyper-cross-linked resin.

The conventional ion exchange process used for recovery of uridine 5'-monophosphate (UMP) from the enzymatic hydrolysate of RNA is environmentally harmful and cost intensive. In this work, an innovative benign process, which comprises adsorption technology and use of a hyper-cross-linked resin as a stationary phase is proposed. The adsorption properties of this kind of resin in terms of adsorption equilibrium as well as kinetics were evaluated. The influences of the operating conditions, i.e., initial UMP concentration, feed flow rate, and bed height on the breakthrough curves of UMP in the fixed bed system were investigated. Subsequently, a chromatographic column model was established and validated for the prediction of the experimentally attained breakthrough curves of UMP and the main impurity component (phosphate ion) with a real enzymatic hydrolysate of RNA as a feed mixture. At the end of this paper, the crystallization of UMP was carried out. The purity of the final product (uridine 5'-monophosphate disodium, UMPNa2) of over 99.5 % was obtained.